Publications

[dura conditions, brain vessels and capillary density in the brains of the european hedgehog (erinaceus europaeus) and the desert hedgehog (erinaceus algirus levaudeni)].		1968	5717246
projections of nucleus caudalis and spinal cord to brainstem and diencephalon in the hedgehog (erinaceus europaeus and paraechinus aethiopicus): a degeneration study.	in the light of hypotheses related to the evolution of pain-carrying systems in mammals, terminal projection fields in brainstem and diencephalon of efferents of nucleus caudalis (nc) of the spinal trigeminal complex and spinal cord were determined in hedgehog by using nauta-gygax and fink-heimer silver techniques for degeneration. unilateral nc lesions resulted in medullary degeneration in the ventral portion of nc contralaterally and bilaterally in cuneate nucleus (cu) and reticular formation. ...	1983	6863599
sertoli cell signaling by desert hedgehog regulates the male germline.	in mammals, testis development is initiated in the embryo in response to the expression of the sex determining gene, sry, in sertoli cell precursors. subsequently, sertoli cells are thought to play a central role in male-specific cell interactions, including those that occur during spermatogenesis. however, the molecular nature of these interactions is poorly understood. desert hedgehog (dhh) encodes a signaling molecule expressed in the testis, but not the ovary, and may therefore play a role i ...	1996	8805249
sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro.	the hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. in the drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. to investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. we found that sonic ...	1997	9236238
regional distribution of sonic hedgehog, patched, and smoothened mrna in the adult rat brain.	in vertebrates, sonic hedgehog (shh), desert hedgehog (dhh), and indian hedgehog (ihh) genes encode a family of morphogen proteins that are implicated in a wide range of signaling activities, particularly during embryonic development. these secreted proteins are proposed to mediate their effects on target cells by interacting with their putative receptor, patched (ptc), and with a seven-pass transmembrane protein, smoothened (smo). however, the roles that these signaling molecules may play in ad ...	1998	9489757
regulation of germ cell death in mammalian gonads.	a large number of primordial germ cells (pgcs), as well as spermatogonia, undergo programmed cell death or apoptosis in the physiological context. in this process, environmental, cytoplasmic and nuclear factors are involved. bcl-2 and its related molecules are known as general regulators of cell death, and some are important for survival of pgcs and spermatogonia. steel factor, a ligand for c-kit, also supports growth and survival of these cells. in addition, bone morphogenetic protein (bmp)8b a ...	1998	9524572
characterization of two patched receptors for the vertebrate hedgehog protein family.	the multitransmembrane protein patched (ptch) is the receptor for sonic hedgehog (shh), a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. current models suggest that binding of shh to ptch prevents the normal inhibition of the seven-transmembrane-protein smoothened (smo) by ptch. according to this model, the inhibition of smo signaling is relieved after mutational inactivation of ptch in the basal cell nevus syndrome. recently, ptch2, a molecule with s ...	1998	9811851
the neurobiology of schwann cells.	this selective review of schwann cell biology focuses on questions relating to the origins, development and differentiation of schwann cells and the signals that control these processes. the importance of neuregulins and their receptors in controlling schwann cell precursor survival and generation of schwann cells, and the role of these molecules in schwann cell biology is addressed. the reciprocal signalling between peripheral glial cells and neurons in development and adult life revealed in re ...	1999	10219747
creating barriers: a new role for schwann cells and desert hedgehog.		1999	10482226
schwann cell-derived desert hedgehog controls the development of peripheral nerve sheaths.	we show that schwann cell-derived desert hedgehog (dhh) signals the formation of the connective tissue sheath around peripheral nerves. mrnas for dhh and its receptor patched (ptc) are expressed in schwann cells and perineural mesenchyme, respectively. in dhh-/- mice, epineurial collagen is reduced, while the perineurium is thin and disorganized, has patchy basal lamina, and fails to express connexin 43. perineurial tight junctions are abnormal and allow the passage of proteins and neutrophils. ...	1999	10482238
schwann cell-derived desert hedgehog signals nerve sheath formation.	reciprocal signaling between axons and schwann cells during development is well established. the contribution of schwann cells to the formation and maintenance of the protective nerve sheaths (endo-, peri-, and epineurium) has been less studied. although mesenchymal cells contribute to all these structures, only perineurial cells contribute to the diffusion barrier between nerves and surrounding tissues. during development, prospective perineurial cells shift from a mesenchymal to epithelial phe ...	1999	10586245
assignment of human desert hedgehog gene (dhh) to chromosome band 12q13.1 by in situ hybridization.		1999	10640830
assignment of desert hedgehog (dhh) to human chromosome bands 12q12-->q13.1 by in situ hybridization.		2000	10773676
a novel mutation of desert hedgehog in a patient with 46,xy partial gonadal dysgenesis accompanied by minifascicular neuropathy.	we describe a patient with 46,xy partial gonadal dysgenesis (pgd) who presented with polyneuropathy. sural nerve pathology revealed peculiar findings characterized by extensive minifascicular formation within the endoneurium and with a decreased density of myelinated fibers. we found, in the patient, a homozygous missense mutation (atg-->acg) at the initiating codon in exon 1 of the desert hedgehog (dhh) gene, which predicts a failure of translation of the gene. the same heterozygous mutation wa ...	2000	11017805
desert hedgehog (dhh) gene is required in the mouse testis for formation of adult-type leydig cells and normal development of peritubular cells and seminiferous tubules.	testes from adult and prepubertal mice lacking the desert hedgehog (dhh:) gene were examined in order to describe further the role of dhh in spermatogenesis because, in a previous report, dhh:-null male mice were shown to be sterile. dhh is a signaling molecule expressed by sertoli cells. its receptor, patched (ptc), has been previously localized to leydig cells and is herein described as being localized also to peritubular cells. two phenotypes of the mice were observed: masculinized (7.5% of d ...	2000	11090455
hedgehog signaling regulation of insulin production by pancreatic beta-cells.	hedgehogs (hhs) are intercellular signaling molecules that regulate tissue patterning in mammalian development. mammalian hhs include sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh). the absence of shh expression is required for the early development of the endocrine and exocrine pancreas, but whether hh signaling functions in the fully developed adult endocrine pancreas is unknown. here we report that hhs ihh and dhh and their receptors patched (ptc) and smoothened are ex ...	2000	11118005
comparative biological responses to human sonic, indian, and desert hedgehog.	a comprehensive comparison of sonic (shh), indian (ihh), and desert (dhh) hedgehog biological activities has not previously been undertaken. to test whether the three higher vertebrate hh proteins have distinct biological properties, we compared recombinant forms of the n-terminal domains of human shh, ihh, and dhh in a variety of cell-based and tissue explant assays in which their activities could be assessed at a range of concentrations. while we observed that the proteins were similar in thei ...	2001	11472839
a developmental study of the desert hedgehog-null mouse testis.	desert hedgehog (dhh) is a cell-signaling molecule that was first discovered in drosophila. a unique testicular phenotype has been described in neonatal and adult dhh-null animals that includes anastomotic seminiferous tubules, pertitubular cell abnormalities, and absence of adult-type leydig cells. in the present study, we addressed the developmental basis for the abnormalities previously described for the adult dhh-null phenotype. the source of dhh is the sertoli cell, and receptors are locali ...	2001	11673255
gli1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: upregulation in transgenic mice blocks spermatogenesis in pachytene.	the zinc finger transcription factor gli1 is the mediator of signaling by members of the hedgehog (hh) family. male mice in which desert hedgehog (dhh), an hh homologue expressed in sertoli cells of the testis, was knocked out are sterile, suggesting that the dhh/gli1 pathway plays a role in spermatogenesis. using an antiserum raised against human gli1, we found that during the first round of spermatogenesis, gli1 expression is initially cytoplasmic, then shifts to the nuclei of sertoli and germ ...	2001	11717126
scip/oct-6, krox-20, and desert hedgehog mrna expression during cns remyelination by transplanted olfactory ensheathing cells.	olfactory ensheathing cells (oecs), although having a separate developmental origin to schwann cells, are able to generate myelin sheaths following transplantation into areas of cns demyelination that are remarkably similar to those made by schwann cells. the transcriptional control of schwann cell myelination has been well documented, in particular the role of scip/oct-6 and krox-20. it is not known, however, whether these transcription factors are also expressed when oecs assume a myelinating ...	2001	11746771
schwann cells as regulators of nerve development.	myelinating and non-myelinating schwann cells of peripheral nerves are derived from the neural crest via an intermediate cell type, the schwann cell precursor [k.r. jessen, a. brennan, l. morgan, r. mirsky, a. kent, y. hashimoto, j. gavrilovic. the schwann cell precursor and its fate: a study of cell death and differentiation during gliogenesis in rat embryonic nerves, neuron 12 (1994) 509-527]. the survival and maturation of schwann cell precursors is controlled by a neuronally derived signal, ...	2002	11755779
minifascicular neuropathy: a new concept of the human disease caused by desert hedgehog gene mutation.	we recently found a patient with 46,xy partial gonadal dysgenesis who presented with polyneuropathy. sural nerve pathology revealed peculiar findings characterized by extensive minifascicular formation and with a decreased density of myelinated fibers. we found in the patient, a homozygous missense mutation at the initiating codon in exon 1 of the desert hedgehog (dhh) gene, which predicts a failure of translation of the gene. these data demonstrate that dhh is a key molecule in both male gonada ...	2002	11990454
desert hedgehog/patched 1 signaling specifies fetal leydig cell fate in testis organogenesis.	establishment of the steroid-producing leydig cell lineage is an event downstream of sry that is critical for masculinization of mammalian embryos. neither the origin of fetal leydig cell precursors nor the signaling pathway that specifies the leydig cell lineage is known. based on the sex-specific expression patterns of desert hedgehog (dhh) and its receptor patched 1 (ptch1) in xy gonads, we investigated the potential role of dhh/ptch1 signaling in the origin and specification of fetal leydig ...	2002	12050120
signals that determine schwann cell identity.	while the signals that direct neural crest cells to choose the glial lineage and generate schwann cell precursors are still obscure, studies both in vivo and in vitro indicate that the survival and differentiation of these cells to form schwann cells is regulated by at least two signals, neuregulin-1 and endothelin. we know little about the signals that cause some immature schwann cells to choose myelin differentiation, while other cells form non-myelinating cells. three transcription factors, s ...	2002	12090403
comparison of hedgehog and patched-1 protein expression in the cranial sutures of craniosynostotic and wild-type rabbits.	craniosynostosis is characterized by premature fusion of the cranial sutures. at the molecular level, mutations in homeobox genes, transcription factors, and growth factor receptors have been implicated in the pathogenesis of this disorder, but the specific etiologic pathways have not yet been elucidated. to further study the molecular biology behind craniosynostosis, perisutural tissues in a unique rabbit model with congenital delayed-onset coronal craniosynostosis were examined for the presenc ...	2002	12142670
changes in the protein expression of hedgehog and patched-1 in perisutural tissues induced by cranial distraction.	with the modern emphasis on minimally invasive therapies, the concept of distraction is being applied in the treatment of craniosynostosis. although specific genetic mutations have been identified in craniosynostotic patients, changes in the gene expression induced by cranial distraction have not yet been explored. the effects of cranial distraction on hedgehog and patched-1 expression were evaluated in a rabbit model for craniosynostosis. rabbits (n = 8) were divided into four groups: affected ...	2002	12142671
desert hedgehog signalling pathway is involved in the proliferation of a malignant peripheral nerve sheath tumour-derived cell line from neurofibromatosis type 1.		2002	12366446
a possible paracrine hedgehog signalling pathway in neurofibromas from patients with neurofibromatosis type 1.	hedgehogs (hhs) and their receptors are involved in organ development as well as in tumorigenesis observed in basal cell carcinoma. among hhs, desert hedgehog secreted from schwann cells mediates the formation of peripheral nerve sheaths. however, there has been no study on the role of hhs and their receptors in tumorigenesis of neurofibromas in neurofibromatosis type 1 (nf1).	2003	12588389
therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy.	hedgehog proteins modulate development and patterning of the embryonic nervous system. as expression of desert hedgehog and the hedgehog receptor, patched-1, persist in the postnatal and adult peripheral nerves, the hedgehog pathway may have a role in maturation and maintenance of the peripheral nervous system in normal and disease states. we measured desert hedgehog expression in the peripheral nerve of maturing diabetic rats and found that diabetes caused a significant reduction in desert hedg ...	2003	12588889
a novel function for hedgehog signalling in retinal pigment epithelium differentiation.	sonic hedgehog is involved in eye field separation along the proximodistal axis. we show that hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. we show that two other hedgehog proteins, banded hedgehog and cephalic hedgehog, related to the mouse indian hedgehog and desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surroun ...	2003	12620982
a tissue-specific knockout reveals that gata1 is not essential for sertoli cell function in the mouse.	the transcription factor gata1 is essential for the development of erythroid cells. consequently, gata1 null mutants die in utero due to severe anaemia. outside the haematopoietic system, gata1 is only expressed in the sertoli cells of the testis. to elucidate the function of gata1 in the testis, we made a sertoli cell-specific knockout of the gata1 gene in the mouse. we deleted a normally functioning 'floxed' gata1 gene in pre-sertoli cells in vivo through the expression of cre from a transgene ...	2003	12954777
mutations in the desert hedgehog (dhh) gene in patients with 46,xy complete pure gonadal dysgenesis.	mutations of sry are the cause of complete pure gonadal dysgenesis (pgd) in 10-15% of patients. in the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. we describe the first report in which three cases of 46,xy complete pgd are attributed to mutations of the desert hedgehog (dhh) gene. dhh was sequenced using genomic dna from paraffin-embedded gonadal tissue from six patients with complete 46,xy pgd. mutatio ...	2004	15356051
characterization of kif7 gene in silico.	sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh) are hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. drosophila costal-2 (cos2) is a hedgehog signaling regulator, interacting with smoothened (smo), cubitus interruptus (ci), fused (fu) and microtubule. kif27 is one of the mammalian orthologs for drosophila cos2. kif7 gene is the paralog of kif27 gene; however, complete coding sequence (cds) ...	2004	15547730
identification and characterization of rat desert hedgehog and indian hedgehog genes in silico.	sonic hedgehog (shh), desert hedgehog (dhh) and indian hedgehog (ihh) bind to patched family receptors (ptch1 and ptch2) to transduce signals to gli1, gli2 and gli3. gli family transcription factors then activate transcription of hedgehog target genes, such as foxe1 and foxm1 encoding forkhead-box transcription factors. hedgehog signaling pathway plays a pivotal role in a variety of human tumors, such as gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, prostate cancer, basal ...	2005	15645142
hedgehog signaling in mouse ovary: indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells.	follicle development in the mammalian ovary requires interactions among the oocyte, granulosa cells, and theca cells, coordinating gametogenesis and steroidogenesis. here we show that granulosa cells of growing follicles in mouse ovary act as a source of hedgehog signaling. expression of indian hedgehog and desert hedgehog mrnas initiates in granulosa cells at the primary follicle stage, and we find induced expression of the hedgehog target genes ptch1 and gli1, in the surrounding pre-theca cell ...	2005	15878962
comparative genomics on sonic hedgehog orthologs.	sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) are key molecules for the integrome network in oncology and regenerative medicine. soluble hedgehog ligands bind to patched receptor to activate smoothened seven-transmembrane receptor with frizzled domain. kif27 and kif7 are human homologs of drosophila costal-2 (cos2), associating with smoothened, gli homolog, fused, and microtubule. smoothened activation leads to gli1, gli2, or gli3-dependent transcription of hedgehog targ ...	2005	16142377
characterization of two new zebrafish members of the hedgehog family: atypical expression of a zebrafish indian hedgehog gene in skeletal elements of both endochondral and dermal origins.	we have characterized two new members of the hedgehog (hh) family in zebrafish, ihha and dhh, encoding for orthologues of the tetrapod indian hedgehog (ihh) and desert hedgehog (dhh) genes, respectively. comparison of ihha and type x collagen (col10a1) expression during skeletal development show that ihha transcripts are located in hypertrophic chondrocytes of cartilaginous elements of the craniofacial and fin endoskeleton. surprisingly, col10a1 expression was also detected in cells forming intr ...	2006	16292774
desert hedgehog-patched 2 expression in peripheral nerves during wallerian degeneration and regeneration.	hedgehog proteins are important in the development of the nervous system. as desert hedgehog (dhh) is involved in the development of peripheral nerves and is expressed in adult nerves, it may play a role in the maintenance of adult nerves and degeneration and regeneration after injury. we firstly investigated the dhh-receptors, which are expressed in mouse adult nerves. the dhh receptor patched(ptc)2 was detected in adult sciatic nerves using rt-pcr, however, ptc1 was undetectable under the same ...	2006	16329124
a heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis.	aetiology of mixed gonadal dysgenesis (mgd) has not been completely elucidated. molecular analyses have failed to demonstrate the presence of mutations in sex-determining region on y chromosome (sry); it has been suggested that these individuals may bear mutations in other genes involved in the testis-determining pathway. desert hedgehog's (dhh) importance regarding male sex differentiation has been demonstrated in various studies we describe here, for the first time, two cases of mgd in which a ...	2005	16390857
multiple gene expression analyses in paraffin-embedded tissues by taqman low-density array: application to hedgehog and wnt pathway analysis in ovarian endometrioid adenocarcinoma.	recent studies have shown the hedgehog and wnt families of signaling proteins to be associated with tumor initiation, growth, and survival. however, these pathways remain unexplored in ovarian endometrioid adenocarcinoma (oea). here, we describe a novel taqman low-density array to examine the expression of 26 and 20 genes in the hedgehog and wnt pathways, respectively, in six matched snap-frozen and formalin-fixed, paraffin-embedded (fpe) oea specimens. expression values were normalized to uninv ...	2006	16436637
the foetal leydig cell-- differentiation, function and regulation.	the foetal leydig cell population arises shortly after testicular differentiation at around 12.5 dpc in the mouse and 6 weeks in the human. these cells function, primarily, to produce androgens which are essential for masculinization of the foetus. the origin of the foetal leydig cells remains uncertain but it has been suggested that adrenocortical cells and foetal leydig cells may share a common origin in an adreno-genital primordium. studies in the mouse are beginning to identify factors such ...	2006	16466528
hedgehog signaling in the normal and diseased pancreas.	the hedgehog (hh) family of genes, sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) encode signaling molecules that regulate multiple functions during organ development and in adult tissues. altered hedgehog signaling has been implicated in disturbed organ development as well as in different degenerative and neoplastic human diseases. hedgehog signaling plays an important role in determination the fate of the mesoderm of the gut tube, as well as in early pancreatic developm ...	2006	16552330
sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis.	fibroblast growth factor 9 (fgf9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the xy gonad, but neither it nor the fgf receptors is expressed sex-specifically. of the sprouty genes encoding antagonists of receptor tyrosine kinases including fgfr, msprouty2 expression was confined to the developing testis and mesonephros. gain of sprouty2 function in the male genital ridge and mesonephros malformed the vas deferens and epididymis, an ...	2006	16675530
the structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog.	we show that desert hedgehog (dhh), a signaling molecule expressed by schwann cells, is essential for the structural and functional integrity of the peripheral nerve. dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating schwann cells, axons, and vasculature and immune cells. myelinated fibers of these mice have a significantly increased (more than two times) number of schmidt-lanterman incisures (slis), and connexin 29, a molecular component of slis, is stron ...	2006	16763045
hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer.	sonic hedgehog (shh) and indian hedgehog (ihh) have cell-specific actions in some organs. only shh has been shown to regulate parietal cell differentiation. this study examined whether shh, 2 other ligands ihh and desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers. the effects of a hedgehog (hh) inhibitor, cyclopamine, were assessed in primary gastric epithelium cultures and gastric cancer cell lines.	2006	16831586
in vivo detection of egr2 binding to target genes during peripheral nerve myelination.	egr2/krox20 is a zinc finger transactivator that regulates a diverse array of genes required for peripheral nerve myelination. although several studies have elucidated the egr2-regulated gene network, it is not clear if egr2 regulates its target genes directly or indirectly through induction of other transactivators. moreover, very few egr2 binding sites have been identified in regulatory elements of myelin genes. to address this issue, we have successfully adapted chromatin immunoprecipitation ...	2006	16923174
elevated anxiety-like and depressive behavior in desert hedgehog knockout male mice.	to investigate the functional role of desert hedgehog (dhh) gene in the nervous system, we examined motor, sensory, learning and memory functions as well as mood in dhh knockout (ko) mice. dhh ko male mice exhibited prolonged immobility time compared with wild-type male mice in the forced swimming test, and showed enhanced inhibition in the vogel's conflict model. these findings suggest that dhh ko male mice exhibited enhanced anxiety and depressive behavior compared with wild-type male mice. in ...	2006	16952407
hedgehog signaling in skeletal development.	hedgehog signaling coordinates a variety of patterning processes during early embryonic development. drosophila hedgehog and its vertebrate orthologs, sonic hedgehog, indian hedgehog, and desert hedgehog, share a generally conserved signal transduction cascade. however, the particular mechanisms by which the lipid-modified molecules specify embryonic tissues differ substantially. vertebrate skeletal patterning is one of the most intensively studied biological processes. during skeletogenesis, so ...	2006	17061262
hedgehog signaling pathway and gastrointestinal stem cell signaling network (review).	hedgehog, bmp/tgfbeta, fgf, wnt and notch signaling pathways constitute the stem cell signaling network, which plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh) bind to ptch1/ptch or ptch2 receptor to release smoothened (smo) signal transducer from patched-dependent suppression. smo then activates ...	2006	17089004
the expression of hedgehog genes (ihh, dhh) and hedgehog target genes (ptc1, gli1, coup-tfii) is affected by estrogenic stimuli in the uterus of immature female rats.	the objective of this study was to investigate the effects of estrogen receptor (er) agonists and an er antagonist on the expression of hedgehog genes (indian hedgehog: ihh; desert hedgehog: dhh) and hedgehog target genes (patched 1: ptc1; glioma-associated oncogene homolog 1: gli1; chicken ovalbumin upstream promoter transcription factor ii: coup-tfii) in the rat uterus. immature female rats were administered once with 17alpha-ethynyl estradiol (ee, an er agonist), propyl pyrazole triole (ppt, ...	2006	17109907
sonic and desert hedgehog signaling in human fetal prostate development.	hedgehog signaling is thought to play an important role in rodent prostate organogenesis and morphogenesis. however, the role of this signaling pathway in human fetal prostate development has not been investigated.	2007	17342747
distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal and adult leydig cell development.	testicular leydig cells produce testosterone and provide the hormonal environment required for male virilization and spermatogenesis. in utero, fetal leydig cells (flcs) are necessary for the development of the wolffian duct and male external genitalia. steroidogenic factor 1 (sf1) is a transcriptional regulator of hormone biosynthesis genes, thus serving a central role in the leydig cell. desert hedgehog (dhh), a sertoli cell product, specifies the flc lineage in the primordial gonad through a ...	2007	17495005
targeting the hedgehog pathway to mitigate treatment resistance.	'hedgehog' (hh) molecules are secretory signaling proteins that were first discovered in drosophila. three hh homologs have been identified in humans including sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh). during embryonic development, the hedgehog (hh) signaling pathway is critical, and it regulates both proliferation and differentiation of various types of stem cells.1this article provides a brief overview of hh signaling, summarizes the correlation between hh signalin ...	2007	17671418
sonic hedgehog regulates hes1 through a novel mechanism that is independent of canonical notch pathway signalling.	aberrant regulation of signalling mechanisms that normally orchestrate embryonic development, such as the hedgehog, wnt and notch pathways, is a common feature of tumorigenesis. in order to better understand the neoplastic events mediated by hedgehog signalling, we identified over 200 genes regulated by sonic hedgehog in multipotent mesodermal cells. widespread crosstalk with other developmental signalling pathways is evident, suggesting a complex network of interactions that challenges the ofte ...	2008	17873912
hedgehog signaling in development and homeostasis of the gastrointestinal tract.	the hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. in this review i discuss the role of hedgehog signaling in the development, postnatal maintenance, and carcinogenesis of the gastrointestinal tract. three mammalian hedgehog genes, sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) have been identified. shh and ihh are important endod ...	2007	17928586
maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development.	maternal cigarette smoking during gestation increases cryptorchidism and hypospadias and reduces testis size and fertility in sons by unknown mechanisms.	2008	18000085
purifying the hedgehog protein and its variants.	the purification of recombinant versions of the n-terminal signaling fragment of sonic hedgehog (shhn) from e. coli, hi-5 insect cells, yeast, and mammalian cell sources reveals diverse post-translational modifications that affect the potency of the purified protein. modifications to the n-terminal cysteine with fatty acyl groups results in significant increases in potency, up to 100-fold, when compared with the unmodified protein. proteolytic clipping at sites near the n-terminus results in ina ...	2007	18025709
plexiform and dermal neurofibromas and pigmentation are caused by nf1 loss in desert hedgehog-expressing cells.	neurofibromatosis type 1 (nf1) mutation predisposes to benign peripheral nerve (glial) tumors called neurofibromas. the point(s) in development when nf1 loss promotes neurofibroma formation are unknown. we show that inactivation of nf1 in the glial lineage in vitro at embryonic day 12.5 + 1, but not earlier (neural crest) or later (mature schwann cell), results in colony-forming cells capable of multilineage differentiation. in vivo, inactivation of nf1 using a dhhcre driver beginning at e12.5 e ...	2008	18242511
leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis.	leydig cells in the rat testis can be specifically ablated with ethane dimethane sulfonate (eds) and will subsequently re-generate. in this study, we have characterized leydig cell re-generation and expression of selected cell-signaling molecules in a germ cell-free model of eds action. this model offers the advantage that re-generation occurs on a stable background without confounding changes from the regressing and repopulating germ cell population. adult rats were treated with busulfan to rem ...	2008	18502897
purification and bioassay of hedgehog ligands for the study of cell death and survival.	the hedgehog (hh) family of secreted ligands-composed of sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh)-possesses many roles during embryonic development, adult homeostasis, and cancer. the specific functions of the hh proteins are intertwined with their requirement as survival factors in hh-responsive cells. however, studies designed to dissect the anti-apoptotic role of hhs have been hindered by the lack of simple approaches to purify large quantities of recombinant lig ...	2008	18603123
expression of hedgehog family genes in the rat uterus during early pregnancy.	hedgehog (hh) plays a pivotal role in various tissues during embryonic development, tissue homeostasis and tumorigenesis. in mammals, hh exists in three homologs: desert hedgehog (dhh), indian hedgehog (ihh) and sonic hedgehog (shh). in this study, we cloned full-length cdnas encoding dhh and ihh from the rat uterus. their amino acid sequences have a high homology with those of the mouse and human. in addition, the changes of hh gene expression in the rat uterus during early pregnancy were analy ...	2008	18612197
antiandrogen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis.	testicular development is an androgen-dependent process, and fetal exposure to antiandrogens disrupts male sexual differentiation. a variety of testicular disorders may result from impaired development of fetal leydig and sertoli cells. we hypothesized that antiandrogenic exposure during fetal development interferes with desert hedgehog (dhh) signaling in the testis and results in impaired leydig cell differentiation. fetal rats were exposed in utero to the antiandrogen flutamide from 10.5 d pos ...	2009	18772241
hedgehog signaling is essential for normal wound healing.	the hedgehog family of morphogens (sonic [shh], indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. although recent work implicates shh in postnatal tissue repair and development, conclusive evidence is lacking. here, we demonstrated the importance of shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the shh signaling cascade, on tissue repair. using a murine-splinted excisional wound model, which attenuates wound c ...	2012	19128247
peripheral neuropathy and 46xy gonadal dysgenesis: a heterogeneous entity.	gonadal dysgenesis with normal male karyotype (46xy) is a sexual differentiation disorder. so far three patients have been reported presenting the association of 46xy gonadal dysgenesis with peripheral neuropathy. examination of sural nerves revealed minifascicle formation in two of them. in one patient, a mutation was found in desert hedgehog homolog (drosophila), a gene important in gonadal differentiation and peripheral nerve development. we studied neuropathological and molecular genetic asp ...	2009	19167223
activation of the hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal leydig cells and female pseudohermaphroditism.	proper cell fate determination in mammalian gonads is critical for the establishment of sexual identity. the hedgehog (hh) pathway has been implicated in cell fate decision for various organs, including gonads. desert hedgehog (dhh), one of the three mammalian hh genes, has been implicated with other genes in the establishment of mouse fetal leydig cells. to investigate whether hh alone is sufficient to induce fetal leydig cell differentiation, we ectopically activated the hh pathway in steroido ...	2009	19268447
hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation.	the hedgehog (hh) pathway is a main regulation cascade in embryonic differentiation. it is also present in adult tissues and unusual expression has been associated with formation of benign and malignant lesions. we examined the presence of the hedgehog pathway in normal and pathological human colon tissue. components investigated include sonic (shh), indian (ihh), and desert hedgehog (dhh), gli1, gli2, gli3, and patched (ptch). pathological tissue samples comprised 23 benign and 20 malignant les ...	2009	19280222
the role of hedgehog signaling during gastric regeneration.	hedgehog signaling plays critical roles during embryonic development. it is also involved in tissue regeneration and carcinogenesis in various adult tissues. moreover, it regulates the maintenance of cancer stem cells and adult stem cells. although hedgehog signaling is important in gastric carcinogenesis, its role in gastric regeneration has not been previously examined. in the present study, we evaluated the expression and roles of hedgehog signaling during gastric regeneration.	2009	19291354
expression of patched-1 and smoothened in testicular meiotic and post-meiotic cells.	desert hedgehog (dhh) signaling plays an essential role in the normal development of the testis and in the process of spermatogenesis. little is known about the involvement in spermatogenesis of the prototypic member of the family, ptc1, which acts to suppress hedgehog signaling through smoothened (smo). here, we have examined the expression of ptc1, smo, and dhh in mouse and rat seminiferous epithelium. our findings demonstrate that ptc1 and smo are expressed by primary spermatocytes and by rou ...	2009	19484749
synthesis and biological evaluation of sant-2 and analogues as inhibitors of the hedgehog signaling pathway.	hedgehog (hh) signaling plays an important role in cell signaling of embryonic development and adult tissue homeostasis. in vertebrates, the hh gene encodes three different unique proteins: sonic hedgehog (shh), desert hedgehog (dhh) and indian hedgehog (ihh). disruption of the hh signaling pathway leads to severe disorders in the development of vertebrates whereas aberrant activation of the hh pathway has been associated with several malignancies including gorlin syndrome (a disorder predisposi ...	2009	19541490
structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein hhip.	hedgehog (hh) morphogens have fundamental roles in development, whereas dysregulation of hh signaling leads to disease. multiple cell-surface receptors are responsible for transducing and/or regulating hh signals. among these, the hedgehog-interacting protein (hhip) is a highly conserved, vertebrate-specific inhibitor of hh signaling. we have solved a series of crystal structures for the human hhip ectodomain and desert hedgehog (dhh) in isolation, as well as hhip in complex with dhh (hhip-dhh) ...	2009	19561611
hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways.	the hedgehog (hh) pathway orchestrates developmental and homeostatic angiogenesis. the three hh isoforms--sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh)--signal through patched-1 (ptch1) and smoothened (smo), to activate the gli transcription factors with a characteristic rank of potency (shh >> ihh > dhh). to dissect the mechanisms through which hh proteins promote angiogenesis, we analyzed processes inherent to vessel formation in endothelial cells. we found that none of ...	2010	20081366
establishment of long-term monolayer cultures of somatic cells from human fetal testes and expansion of peritubular myoid cells in the presence of androgen.	the somatic (sertoli cell (sc), leydig cell (lc), and peritubular myoid (ptm) cell) cells play key roles in development of the fetal testis. we established monolayer cultures from second trimester human testes and investigated the pattern of expression of cell-lineage characteristic mrnas. expression of some sc-associated genes (sry, sox9, wt1, gata4, and sf1) was detectable up to and including passage 3 (p3), while others (anti-müllerian hormone; desert hedgehog) present prior to dissociation w ...	2010	20089665
origin, development and regulation of human leydig cells.	sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. since leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. the present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of huma ...	2010	20190545
human plasma very low density lipoprotein carries indian hedgehog.	hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. in drosophila, hedgehog transport via lipophorins is relevant for development, but neither the presence nor a function for a mammalian hedgehog carried by human plasma lipoproteins has been established. we investigated the presence of hedgehog on lipoprotein particl ...	2010	20839884
effects of low intensity pulsed ultrasound on rat schwann cells metabolism.	the effects of low intensity pulsed ultrasound to tenocytes and osteocytes are well understood and applied clinically. however, its effects on cultured schwann cells are still not well elucidated. this study was designed to elucidate the effects of low intensity pulsed ultrasound on cultured schwann cells and their possible molecular mechanism. schwann cells were harvested from sciatic nerves of 3-day-old sprague-dawley rats. low intensity pulsed ultrasound stimulator (frequency: 1 mhz, duration ...	2010	20946299
a missense mutation of the dhh gene is associated with male pseudohermaphroditic rats showing impaired leydig cell development.	development of the male gonads is a complex process with interaction of various cells in the gonads including germ, sertoli, leydig, and myoid cells. tf is a mutant rat strain showing male pseudohermaphroditism, with agenesis of leydig cells and androgen deficiency controlled by an autosomal single recessive gene (mp). the mp locus was mapped on the distal region of rat chromosome 7 by linkage analysis, but the gene responsible for the mp mutation has not been identified. in this study, we perfo ...	2010	21062903
sox9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog.	we investigated the expression of sox9, a transcription factor linked to the hedgehog pathways, and desert hedgehog, previously shown to be expressed in a malignant peripheral nerve sheath tumor cell line, in neurofibromatosis 1 tumors (neurofibromas and malignant peripheral nerve sheath tumor), and in a group of sporadic spindle cell sarcomas. we found that sox9 was expressed in schwann cells from neurofibromatosis 1 tumors, and was significantly up-regulated in malignant peripheral nerve sheat ...	2010	21193222
identification of novel sry mutations and sf1 (nr5a1) changes in patients with pure gonadal dysgenesis and 46,xy karyotype.	primary amenorrhea due to 46,xy disorders of sexual development (dsd) is complex with the involvement of several genes. karyotyping of such patients is important as they may develop dysgerminoma and molecular analysis is important to identify the underlying mechanism and explore the cascade of events occurring during sexual development. the present study was undertaken for the genetic analysis in seven patients from five families presenting with primary amenorrhea and diagnosed with pure gonadal ...	2011	21242195
dual roles of the cardin-weintraub motif in multimeric sonic hedgehog.	the fly morphogen hedgehog (hh) and its mammalian orthologs, sonic, indian and desert hedgehog are secreted signaling molecules that mediate tissue patterning during embryogenesis and function in tissue homeostasis and regeneration in the adult. the function of all hh family members is regulated at the levels of morphogen multimerization on the surface of producing cells, multimer release, multimer diffusion to target cells and signal reception. these mechanisms are all known to depend on intera ...	2011	21572042
pharmacological inhibition of the hedgehog pathway prevents human rhabdomyosarcoma cell growth.	the hedgehog pathway functions as an organizer in embryonic development. recent studies have shown that mutation of the ptch1 gene involved in the hedgehog pathway affects rhabdomyosarcoma development. however, the expression of hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. in addition, the effect of pharmacological inhibition of the hedgehog pathway is not known. we investigated the expression of the genes involved in the hedgehog pathway using human rh ...	2011	21674124
novel homozygous mutations in desert hedgehog gene in patients with 46,xy complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods.	male to female sex reversal in patients with 46,xy karyotype results from the failure of development of testis which may be due to mutations in the sry gene. only 10-15% of cases of 46,xy gonadal dysgenesis are accounted for by different types of mutations in the sry gene. hence, majority of such patients may have mutations in other genes involved in the testicular differentiation pathway. besides sry, other autosomal and x-linked genes are also involved in sexual development during embryogenesi ...	2011	21816240
Hedgehog signalling promotes germ cell survival in the rat testis.	Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by ...	2011	21893610
hedgehog signaling regulates myelination in the peripheral nervous system through primary cilia.	myelination is an essential prerequisite for the nervous system to transmit an impulse efficiently by a saltatory conduction. in the peripheral nervous system (pns), schwann cells (scs) engage in myelination. however, a detailed molecular mechanism underlying myelination still remains unclear. in this study, we hypothesized that the primary cilia of scs are the regulators of hedgehog (hh) signaling-mediated myelination. to confirm our hypothesis, we used mouse dorsal root ganglion (drg)/sc co-cu ...	2011	22101064
Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial.	ABSTRACT: BACKGROUND: Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the ta ...	2011	22132805
rickettsiae in arthropods collected from the north african hedgehog (atelerix algirus) and the desert hedgehog (paraechinus aethiopicus) in algeria.	hedgehogs have become a popular pet despite their potential role in zoonotic disease transmission. we conducted an entomological study in a mountainous region of northeast algeria in which we collected 387 fleas (archeopsylla erinacei) and 342 ticks (rhipicephalus sanguineus and haemaphysalis erinacei) from paraechinus aethiopicus and atelerix algirus hedgehogs. of the hedgehogs sampled, 77.7% and 91% were infested with fleas and ticks, respectively. significantly more ticks and fleas were colle ...	2012	22222114
interaction between hedgehog signalling and pax6 dosage mediates maintenance and regeneration of the corneal epithelium.	to investigate the roles of intracellular signaling elicited by hedgehog (hh) ligands in corneal maintenance and wound healing.	2012	22275805
hedgehog signaling.	the original hedgehog (hh) gene was found in drosophila and named for the appearance of a mutant phenotype which causes an embryo to be covered with pointy denticles, thus resembling a hedgehog. the hedgehog family consists of sonic hedgehog (shh), desert hedgehog (dhh), and indian hedgehog (ihh). shh is found in vertebrates and the best studied ligand of the hedgehog signaling pathway (gilbert, 2000). it plays an important role in regulating vertebrate organogenesis, such as in the growth of di ...	2012	22391297
regulation of murine normal and stress-induced erythropoiesis by desert hedgehog.	the function of hedgehog signaling in hematopoiesis is controversial, with different experimental systems giving opposing results. here we examined the role of desert hedgehog (dhh) in the regulation of murine erythropoiesis. dhh is one of 3 mammalian hedgehog family proteins. dhh is essential for testis development and schwann cell function. we show, by analysis of dhh-deficient mice, that dhh negatively regulates multiple stages of erythrocyte differentiation. in dhh-deficient bone marrow, the ...	2012	22461491
desert hedgehog links transcription factor sox10 to perineurial development.	schwann cells are the main glial cell type in the pns. they develop along nerves during embryogenesis and rely on the hmg domain containing sox10 transcription factor for specification, lineage progression, and terminal differentiation. sox10 deletion in immature schwann cells caused peripheral nerve defects in mice that were not restricted to this glial cell type, although expression in the nerve and gene loss were. formation of the perineurium as the protecting sheath was, for instance, heavil ...	2012	22514309
[desert hedgehog regulates the proliferation and differentiation of leydig cells: an update].	hedgehog signaling pathway plays an important role in regulating the development of endocrine glands. desert hedgehog (dhh) has become a recent focus for its regulation of testis development, especially of leydig cells. dhh, as a sertoli cell product, regulates the proliferation and differentiation of leydig cell lineage and functions to secrete testosterone through a paracrine signaling mechanism. testosterone, as the most important sex hormone of the male, plays a critical role in testis devel ...	2012	22568218
autocrine sonic hedgehog attenuates inflammation in cerulein-induced acute pancreatitis in mice via upregulation of il-10.	hedgehog signaling plays critical roles in pancreatic oncogenesis and chronic pancreatitis, but its roles in acute pancreatitis (ap) are largely ambiguous. in this study, we provide evidence that sonic hedgehog (shh), but neither desert hedgehog (dhh) nor indian hedgehog (ihh), is the main protein whose expression is activated during the development of cerulein-induced acute pancreatitis in mice, and the shh serves as an anti-inflammation factor in an autocrine manner. blocking autocrine shh sig ...	2012	22956998
mouse testis development and function are differently regulated by follicle-stimulating hormone receptors signaling during fetal and prepubertal life.	it is currently admitted that follicle-stimulating hormone (fsh) is physiologically involved in the development and function of fetal/neonatal sertoli cells in the rat but not the mouse. however, fsh is produced by both species from late fetal life onwards. we thus reinvestigated the role of fsh in mouse testis development at day 0 (birth) 6, 8 and 10 post-partum (dpp) by using mice that lack functional fsh receptors (fsh-r(-/-)). at birth, the number and proliferative index of sertoli cells wer ...	2012	23300903
conditional inactivation of pten with egfr overexpression in schwann cells models sporadic mpnst.	the genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (nf1-)associated or sporadic malignant peripheral nerve sheath tumors (mpnsts) remain unclear. it is hypothesized that many genetic changes are involved in transformation. recently, it has been shown that both phosphatase and tensin homolog (pten) and epidermal growth factor receptor (egfr) play important roles in the initiation of peripheral nerve sh ...	2012	23319880
desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.	blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. desert hedgehog (dhh), one of the hedgehog family members, is expressed by schwann cells of peripheral nerves.	2013	23343527
a review of hedgehog signaling in cranial bone development.	during craniofacial development, the hedgehog (hh) signaling pathway is essential for mesodermal tissue patterning and differentiation. the hh family consists of three protein ligands: sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh), of which two are expressed in the craniofacial complex (ihh and shh). dysregulations in hh signaling are well documented to result in a wide range of craniofacial abnormalities, including holoprosencephaly (hpe), hypotelorism, and cleft lip/pa ...	2013	23565096
in vitro and molecular modeling analysis of two mutant desert hedgehog proteins associated with 46,xy gonadal dysgenesis.	mutations of desert hedgehog (dhh) have been associated to 46,xy pure gonadal dysgenesis (pgd) and to mixed gonadal dysgenesis (mgd); however, there have been no functional studies of mutations described in dhh. to determine if mutations p.l162p and δ1086delg yield functional impairment, we performed in vitro and in silico analysis of both dhh mutants. in complementary dna of dhh, we performed site-directed mutagenesis, which was confirmed by dna sequencing. protein extracts were obtained from h ...	2013	23786321
the intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.	in vertebrates, canonical hedgehog (hh) pathway activation requires smoothened (smo) translocation to the primary cilium (pc), followed by a gli-mediated transcriptional response. in addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of smo signalling. the hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood. this study aimed to characterise hh pat ...	2014	23978713
serum level of desert hedgehog protein in autism spectrum disorder: preliminary results.	to investigate the role of desert hedgehog (dhh) in a neurodevelopmental disorder known as autism.	2014	24009062
dhh-rhebl1 fusion transcript: a novel recurrent feature in the new landscape of pediatric cbfa2t3-glis2-positive acute myeloid leukemia.	childhood acute myeloid leukemia (aml) is a clinically and genetically heterogeneous malignant disease. despite improvements in outcome over the past decades, the current survival rate still is approximately 60-70%. cytogenetic, recurrent genetic abnormalities and early response to induction treatment are the main factors predicting clinical outcome. while the majority of children carry recurrent chromosomal translocations, 20% of patients do not show any recognizable cytogenetic alteration and ...	2013	24127550
mutation analysis of mitogen activated protein kinase 1 gene in indian cases of 46,xy disorder of sex development.	determination of sex is the result of cascade of molecular events that cause undifferentiated bipotential gonad to develop as a testis or an ovary. a series of genes such as sry, steroidogenic factor-1 (sf1), ar, srd5 α, desert hedgehog (dhh) etc., have been reported to have a significant role in development of sex in the fetus and secondary sexual characteristics at the time of puberty. recently, mitogen activated protein kinase kinase kinase 1 (map3k1) gene was found to be associated with 46, ...	0	24497709