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PubMed1999

Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.

Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409-3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-&Dgr;-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.

Animals↗
PubMed2002

Fused-dependent Hedgehog signal transduction is required for somatic cell differentiation during Drosophila egg chamber formation.

The fused gene encodes a serine/threonine kinase involved in Hedgehog signal transduction during Drosophila embryo and larval imaginal disc development. Additionally, fused mutant females exhibit reduced fecundity that we report here to be associated with defects in three aspects of egg chamber formation: encapsulation of germline cysts by prefollicular cells in the germarium, interfollicular stalk morphogenesis and oocyte posterior positioning. Using clonal analysis we show that fused is required cell autonomously in prefollicular and pre-stalk cells to control their participation in these aspects of egg chamber formation. In contrast to what has been found for Hedgehog and other known components of Hedgehog signal transduction, we show that fused does not play a role in the regulation of somatic stem cell proliferation. However, genetic interaction studies, as well as the analysis of the effects of a partial reduction in Hedgehog signaling in the ovary, indicate that fused acts in the classical genetic pathway for Hedgehog signal transduction which is necessary for somatic cell differentiation during egg chamber formation. Therefore, we propose a model in which Hedgehog signals at least twice in germarial somatic cells: first, through a fused-independent pathway to control somatic stem cell proliferation; and second, through a classical fused-dependent pathway to regulate prefollicular cell differentiation.

Animals↗
PubMed2002

Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney.

Signaling by the ureteric bud epithelium is essential for survival, proliferation and differentiation of the metanephric mesenchyme during kidney development. Most studies that have addressed ureteric signaling have focused on the proximal, branching, ureteric epithelium. We demonstrate that sonic hedgehog is expressed in the ureteric epithelium of the distal, non-branching medullary collecting ducts and continues into the epithelium of the ureter -- the urinary outflow tract that connects the kidney with the bladder. Upregulation of patched 1, the sonic hedgehog receptor and a downstream target gene of the signaling pathway in the mesenchyme surrounding the distal collecting ducts and the ureter suggests that sonic hedgehog acts as a paracrine signal. In vivo and in vitro analyses demonstrate that sonic hedgehog promotes mesenchymal cell proliferation, regulates the timing of differentiation of smooth muscle progenitor cells, and sets the pattern of mesenchymal differentiation through its dose-dependent inhibition of smooth muscle formation. In addition, we also show that bone morphogenetic protein 4 is a downstream target gene of sonic hedgehog signaling in kidney stroma and ureteral mesenchyme, but does not mediate the effects of sonic hedgehog in the control of mesenchymal proliferation.

Animals↗
PubMed2002

Cerebellar proteoglycans regulate sonic hedgehog responses during development.

Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As sonic hedgehog is expressed in the cerebellum throughout life it is not clear why proliferation occurs only in the early postnatal period and only in the external granule cell layer. We asked whether heparan sulfate proteoglycans might regulate sonic hedgehog-induced proliferation and thereby contribute to the specialized proliferative environment of the external granule cell layer. We identified a conserved sequence within sonic hedgehog that is essential for binding to heparan sulfate proteoglycans, but not for binding to the receptor patched. Sonic hedgehog interactions with heparan sulfate proteoglycans promote maximal proliferation of postnatal day 6 granule cells. By contrast, proliferation of less mature granule cells is not affected by sonic hedgehog-proteoglycan interactions. The importance of proteoglycans for proliferation increases during development in parallel with increasing expression of the glycosyltransferase genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate proteoglycans, synthesized by exostosins, may be critical determinants of granule cell proliferation.

Amino Acid Sequence↗
PubMed2005

Nondestructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): I. Relationships between concentrations of metals and arsenic in hair, spines, and soil.

Conventional metal exposure assessment in terrestrial mammals is generally based on organ analyses of sacrificed animals. Few studies on mammals use nondestructive methodologies despite the growing ethical concern over the use of destructive sampling. Nondestructive methods involve minimal stress to populations and permit successive biomonitoring of the same populations and individuals. In the present study we assessed metal exposure of hedgehogs (Erinaceus europaeus) by investigating relationships between concentrations of metals (Ag, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn) and As in soil samples and in hair and spines of hedgehogs. Samples were collected in seven study sites along a metal pollution gradient, characterized by decreasing total soil Ag, As, Cd, Cu, Ni, and Pb concentrations with increasing distance from a nonferrous metallurgic factory. For a number of elements, soil contamination was related both to distance to the smelter and to habitat. Soil concentrations were positively related to levels in hair and spines for Ag, As, Cd, and Pb and thus to hedgehog exposure. Metal concentrations in soil did not relate to metal concentrations in hair and spines for essential elements (e.g., Cu, Fe, Mn, Ni, and Zn), except Co in hair and soil. Our results demonstrate that, at least for nonessential elements, concentrations in soils can be used to predict contamination of these elements in hedgehogs or vice versa. Furthermore, hedgehog exposure increased toward the smelter and was higher for hedgehogs foraging in grasslands than for animals foraging in the forest. Moreover, we believe that hair and spines are promising tools in terrestrial wildlife exposure assessment studies of metals and As.

Analysis of Variance↗
PubMed2003

The epidemiology and mating behavior of Arthroderma benhamiae var. erinacei in household four-toed hedgehogs (Atelerix albiventris) in Japan.

An epidemiological survey of Trichophyton mentagrophytes var. erinacei in the household hedgehog and other rodents was made between January 17, 2002 and February 28, 2002 in Japan. Quills and hairs were collected from sources identified via the internet. The fungus was isolated only from the quills of four-toed hedgehogs (7/18; 39%) from Kanto to Kyushu regions. Isolates were examined morphologically, physiologically and genetically, and identified as T. mentagrophytes var. erinacei anamorph. The isolates were also genetically compared with European hedgehog (Erinaceus europeus)-borne T. mentagrophytes var. erinacei and Kenyan hedgehog (Aterelix albiventris)-borne Arthroderma benhamiae, and their genotypes of the ITS1-5.8S-ITS2 rDNA were all identical. The isolates were crossed with A. benhamiae Americano-European race and African race, A. vanbreuseghemii and A. simii, with the result that they mated only with African race (+) or (-). Mating types of the isolates were (+) in 6 isolates and (-) in one. An intra-isolate mating between one of the 6 plus isolates and the minus one formed abundant mature gymnothesia, the mating type ratio of the F1 progeny was approximately 1:1, and the sib crossings of F1 progeny produced abundant fertile gymnothesia. The present study revealed that the intra-Japanese hedgehog-borne isolate crossing showed complete fertility and that the sexual degeneration pointed out by Takashio (Mycologia 71: 968-976, 1979) did not exist. Two pairs of mating, (+) and (-) mating types of Japanese isolates with (-) and (+) tester strains of A. benhamiae African race formed less gymnothesia, mating type ratios were unbalanced, and sib crossings of F1 progeny produced small gymnothesia containing a low number of asci, pseudogymothesia, or none, respectively. These results show that A. benhamiae var. erinacei, the teleomorph of T. mentagrophytes var. erinacei, belongs to a different mating group (e.g. hedgehog race) than the Americano-European and African races in A. benhamiae.

Animals↗
PubMed2005

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 target genes. Here, comparative proteomics analyses and comparative genomics analyses on SHH orthologs were performed by using bioinformatics. Human SHH representative transcript was assembled by using BX461534 EST, NM_000193.2 RefSeq, AA503654 EST, and AC078834.5 genome sequence. Human SHH mRNA was expressed in fetal brain, infant brain, and also in colorectal cancer. Chimpanzee SHH gene, consisting of three exons, was located within AC147335.2 genome sequence. Human SHH and chimpanzee SHH (462 aa) showed E284G and T416P amino-acid substitutions. Vertebrate SHH orthologs shared the common domain architecture, consisting of N-terminal signal peptide, Hedgehog signaling domain, Hint domain, and C-terminal HPLGMxxxxS motif. Evolutionarily conserved SHH promoter region (nucleotide position 104429-104083 of human genome sequence AC078834.5) was identified. Double bHLH binding sites, CCAAT box, and TATA box were conserved among human SHH promoter, chimpanzee SHH promoter, rat Shh promoter, and mouse Shh promoter.

Amino Acid Motifs↗
PubMed2005

[Expression of hedgehog proteins in periampullary cancer].

BACKGROUND/AIMS: Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma. METHODS: We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%). RESULTS: All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001). CONCLUSIONS: Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Noradrenergic and dopaminergic systems in the central nervous system of the hedgehog (Erinaceus europaeus).

The distribution of the noradrenaline (NA)- and dopamine (DA)-containing neuronal structures in the central nervous system of the hedgehog (Erinaceus europaeus), a phylogenetically old mammalian species, was immunocytochemically studied employing antibodies directed against the catecholamines (CA) themselves. Groups of DA cell bodies observed in this study were similar to those present in other species but the distributional map of the NA-containing cell bodies exhibited some peculiarities. Prominent among them were the absence of the A3 group and the paucity of CA cells in the A2 group. DA neurons in the hypothalamus, apart from the densely populated paraventricular and arcuate nuclei, were fewer and less widely distributed than in other species. In the hedgehog mesencepha- Ion, in contrast to what has been described in other species, the major DA cell group was present in the ventral tegmental area. CA immunoreactive fibers were widely distributed in the CNS of the hedgehog. However, similarly to what has been observed in other species, terminal fields of DA neurons were much more restricted when compared to those of the NA neurons. The neocortical DA projection system of the hedgehog appeared less developed but organized similar to that of the rat, and even less developed than that of the primates. The lack of profound regional and laminar variations in the density of cortical NA fibers in the hedgehog enhances the suggestion that the elaboration and differentiation of the NA cortical system parallels the phylogenetic development of the cortex. In the brainstem, interspecies differences in the distribution of the CA fibers were found to concern primarily some hypothalamic areas (medial preoptic area, suprachiasmatic nucleus, arcuate nucleus). Such differences in the thalamus concerned the NA innervation and they were notably present in the visual thalamic nuclei (dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus). In the spinal cord, which was found to receive fewer CA afferents than those found in other species, the density of the DA fibers was much lower than that of the NA axons. In addition to the CNS areas that have been described in other species to receive catecholaminergic innervation, the present study showed that both types of catecholaminergic fibers are distributed in the choroid plexus and along the ventricular wall of the brain ventricles and the central canal of the hedgehog.

Adrenergic Fibers↗
PubMed1998

Hedgehog rehabilitation in perspective.

Thousands of hedgehogs are taken into care each year, mostly injured animals or late-born young unlikely to survive hibernation. Many are returned to the wild, but until recently there was little information about their welfare, behaviour or survival after release. A review of three studies undertaken in different regions of Britain, showed that the majority of 33 released adults and juveniles adapted quickly to life in the wild despite the juveniles having been raised in captivity. They found food readily, made nests and rapidly learned their way about. They all lost weight initially but, after two three weeks, stabilised at a similar weight to wild animals. The hedgehogs which were heaviest at release lost the greatest percentage of their bodyweight, suggesting they had become overweight in captivity. The hedgehogs which were known not to have survived at least six weeks after release included three road casualties and three eaten by badgers. Although wild hedgehogs may die in the same ways, it is possible that the released hedgehogs' susceptibility to such dangers may be increased by their becoming tame during captivity. However, the high survival rate suggests that the release of rehabilitated hedgehogs back into the wild is worthwhile.

Animal Welfare↗
PubMed2000

Expression of Sonic hedgehog and retinal opsin genes in experimentally-induced myopic chick eyes.

The purpose of this study was to evaluate changes in the expression of different genes in chick retinal tissues after induction of experimental myopia and to evaluate the roles of these genes in the regulation of postnatal eye growth and myopia. Form-deprivation using occlusive goggles and hyperopic defocus by negative spectacle lenses were used to induce myopia in hatched chicks. Expression levels of Sonic hedgehog, its receptor complex, and other retinal cell genes were evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Levels of Sonic hedgehog protein were further evaluated by Western blot analysis. The induction of myopia caused significant increase in expression of Sonic hedgehog mRNA and protein and increased expression of blue and red opsin mRNA. In contrast, the expression of mRNA for Sonic hedgehog receptor complex (Patched-Smoothened), rhodopsin, vimentin, green opsin, violet opsin, and HPC-1 were unaffected by the induction of myopia. The increase in expression of Sonic hedgehog in chick retinas in experimentally-induced myopia suggests involvement in the retina control of postnatal eye growth. Furthermore, Sonic hedgehog may influence the expression of blue and red opsins under myopic conditions.

Animals↗
PubMed1988

Requirements for hedgehog, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila.

Mutations of the hedgehog gene are generally embryonic lethal, resulting in a lawn of denticles on the ventral surface. In strong alleles, no segmentation is obvious and the anteroposterior polarity of ventral denticles is lost. Temperature shift analysis of a temperature-sensitive allele indicates an embryonic activity period for hedgehog between 2.5 and 6 hr of embryonic development (at 25 degrees) and a larval/pupal period from 4 to 7 days of development (at 25 degrees). Mosaic analysis of hedgehog mutations in the adult cuticle indicates a series of defined defects associated with the failure of appropriate hedgehog expression. In particular, defects in the distal portions of the legs and antenna occur in association with homozygous hedgehog clones in the posterior compartment of those structures. Because the defects are associated with homozygous clones, but are not co-extensive, a type of "domineering" nonautonomy is proposed for the activity of the hedgehog gene.

Alleles↗
PubMed2006

An unusual choanoflagellate protein released by Hedgehog autocatalytic processing.

Hedgehog proteins are important cell-cell signalling proteins utilized during the development of multicellular animals. Members of the hedgehog gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual hedgehog-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes evolved by fusion of two distinct genes.

Amino Acid Sequence↗
PubMed1995

NADPH-diaphorase active and calbindin D-28k-immunoreactive neurons and fibers in the olfactory bulb of the hedgehog (Erinaceus europaeus).

The hedgehog, a macrosomatic insectivore with an extraordinary development of the olfactory structures, has a crucial value for any phylogenetic or comparative study in mammals. The distribution pattern and morphology of NADPH-diaphorase-active and calbindin D-28k-immunoreactive neurons were studied in the main and accessory olfactory bulbs of the hedgehog. NADPH-diaphorase (ND) staining was carried out by a direct histochemical method, and the calbindin D-28k (CaBP) immunoreaction by using a monoclonal antibody and the avidin-biotin-immunoperoxidase method. The possible coexistence of both markers was determined by sequential histochemical-immunohistochemical double labeling of the same sections. Specific neuronal populations were positive for both ND and CaBP markers. No cell colocalized both stains in the hedgehog olfactory bulb. A subpopulation of olfactory fibers, and a subpopulation of olfactory glomeruli, located on the medial side, were positive for ND. Surrounding both the ND-positive and ND-negative glomeruli, there were ND- and CaBP-positive periglomerular cells, the latter group being much more abundant. A subpopulation of superficial short-axon cells was CaBP positive but, contrary to what is observed in rodents, this neuronal type was always ND negative. In addition, three neuronal types were observed in the GL-EPL border after CaBP immunostaining. These neuronal types have not been previously described either in the hedgehog or in the rodent olfactory bulb. Horizontal cells and vertical cells of Cajal were also observed after both ND and CaBP labeling. Distinct groups of ND- and CaBP-positive cells, differing in size, shape, dendritic branching pattern, and staining intensity, were distinguished in the granule cell layer and in the white matter. The large and medium-sized cells were identified as a very heterogeneous population of deep short-axon cells, whereas a subpopulation of granule cells was ND positive. The accessory olfactory bulb showed ND staining in all vomeronasal fibers and glomeruli, and in subpopulations of periglomerular cells, granule cells, and deep short-axon cells. The CaBP immunolabeling was more restricted and located in subpopulations of periglomerular cells and in deep short-axon cells. These results indicate different and more complex ND and CaBP staining patterns in the hedgehog olfactory bulb than those previously described in rodents, including the presence of specific, chemically and morphologically defined new neuronal types.

Amino Acid Oxidoreductases↗
PubMed2005

Hedgehog signaling controls Soma-Germen interactions during Drosophila ovarian morphogenesis.

The genetic analysis of Drosophila adult oogenesis has provided insights into the molecular mechanisms that control cell proliferation, differentiation, migration, and intercellular signaling. However, little is known about the larval and pupal cellular events leading to the formation of the highly organized adult ovary, which is composed of ovarioles each containing germline cells enveloped by specialized somatic cells. We describe here the presence of ovarioles devoid of any germ cells in adult females mutant for fused, which encodes a Hedgehog signal transducing serine/threonine kinase. We show that this phenotype corresponds to a requirement for fused function for the organization of germ cells with respect to ovarian somatic cells during ovariole formation specifically during pupal stages and provide some evidence by means of clonal analysis suggesting that fused function may be necessary in the germline. hedgehog is expressed specifically in somatic terminal filament cells in pupal ovaries, and females bearing hedgehog strong loss-of-function mutations also exhibit aberrant germ cell distribution and formation of agametic ovarioles. These results indicate a positive role for Fused in the transduction of somatic Hedgehog signaling instructing ovariole morphogenesis. We also provide evidence for the use of noncanonical Hedgehog signal transducer(s) within germline cells.

Alleles↗
PubMed2006

Hedgehog signaling is activated in subsets of esophageal cancers.

The hedgehog pathway plays a critical role in the development of the foregut. However, the role of the hedgehog pathway in primary esophageal cancers is not well studied. Here, we report that elevated expression of hedgehog target genes occurs in 14 of 22 primary esophageal cancers. The hedgehog signaling activation is not associated with tumor subtypes, stages, or differentiation. While the sonic hedgehog (Shh) transcript is localized to the tumor tissue, expression of Gli1 and PTCH1 is observed both in the tumor and in the stroma. We discovered that 4 esophageal squamous cell carcinomas, which overexpress Shh, have genomic amplification of the Shh gene. Treatment of esophageal cancer cells with smoothened antagonist, KAAD-cyclopamine, or the neutralizing antibodies of Shh reduces cell growth and induces apoptosis. Overexpression of Gli1 under the CMV promoter renders these cells resistant to the treatments. Thus, our results indicate that elevated expression of Shh and its target genes is quite common in esophageal cancers. Our data also indicate that downregulation of Gli1 expression may be an important mechanism by which KAAD-cyclopamine inhibits growth and induces apoptosis in esophageal cancer cells.

Aged↗
PubMed1997

Involvement of Sonic hedgehog in the cell growth of LK-2 cells, human lung squamous carcinoma cells.

Mutation of the Patched gene has been detected in human inherited basal cell nevus syndrome (BCNS) and sporadic basal cell carcinomas (BCC), suggesting a strong relation between a Sonic hedgehog-Patched signal and cell proliferation. In the present study, we demonstrate that Sonic hedgehog is expressed in human lung squamous carcinoma (LK-2 and EBC-1) and some adenocarcinoma cell lines. The expression of Sonic hedgehog is also detected in the human lung squamous carcinoma tissues, but not in the normal lung tissue of the same patient. The N-terminal region of Sonic hedgehog stimulates the incorporation of BrdU into LK-2 cells and stimulates their cell growth, while anti-Shh-N inhibits their cell growth. These results suggest that a Sonic hedgehog signal is involved in the cell growth of LK-2 cells.

Amino Acid Sequence↗
PubMed2000

Function for Hedgehog genes in zebrafish retinal development.

The hedgehog (hh) genes encode secreted signaling proteins that have important developmental functions in vertebrates and invertebrates. In Drosophila, expression of hh coordinates retinal development by propagating a wave of photoreceptor differentiation across the eye primordium. Here we report that two vertebrate hh genes, sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh), may perform similar functions in the developing zebrafish. Both shh and twhh are expressed in the embryonic zebrafish retinal pigmented epithelium (RPE), initially in a discrete ventral patch which then expands outward in advance of an expanding wave of photoreceptor recruitment in the subjacent neural retina. A gene encoding a receptor for the hedgehog protein, ptc-2, is expressed by retinal neuroepithelial cells. Injection of a cocktail of antisense (alphashh/alphatwhh) oligonucleotides reduces expression of both hh genes in the RPE and slows or arrests the progression of rod and cone photoreceptor differentiation. Zebrafish strains known to have mutations in Hh signaling pathway genes similarly exhibit retardation of photoreceptor differentiation. We propose that hedgehog genes may play a role in propagating photoreceptor differentiation across the developing eye of the zebrafish.

Animals↗