Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hedgehogs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1996

A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities.

Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly development and has a close functional relationship with hedgehog. We have isolated a complete human PATCHED cDNA sequence, which encodes a putative protein of 1296 amino acids, and displays 39% identity and 60% similarity to the Drosophila PATCHED protein. Hydropathy analysis suggests that human PATCHED is an integral membrane protein with a pattern of hydrophobic and hydrophilic stretches nearly identical to that of Drosophila patched. In the developing mouse embryo, patched is initially detected within the ventral neural tube and later in the somites and limb buds. Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity. The results show that patched is expressed in target tissues of sonic hedgehog, a murine homolog of Drosophila hedgehog suggesting that patched/hedgehog interactions have been conserved during evolution. Human PATCHED maps to human chromosome 9q22.3, the candidate region for the nevoid basal cell carcinoma syndrome. Patched expression is compatible with the congenital defects observed in the nevoid basal cell carcinoma syndrome.

Amino Acid Sequence↗
PubMed1997

Post-translational processing and renal expression of mouse Indian hedgehog.

The full-length mouse Indian hedgehog (Ihh) cDNA was cloned from an embryonic 17.5-day kidney library and was used to study the post-translational processing of the peptide and temporal and spatial expression of the transcript. Sequence analysis predicted two putative translation initiation sites. Ihh translation was initiated at both initiation sites when expressed in an in vitro transcription/translation system. Expression of an Ihh mutant demonstrated that the internal translation initiation site was sufficient to produce the mature forms of Ihh. Ihh post-translational processing proceeded in a fashion similar to Sonic and Drosophila hedgehog; the unprocessed form underwent signal peptide cleavage as well as internal proteolytic processing to form a 19-kDa amino-terminal peptide and a 26-kDa carboxyl-terminal peptide. This processing required His313 present in a conserved serine protease motif. Ihh transcript was detected by in situ RNA hybridization as early as 10 days postcoitum (dpc) in developing gut, as early as 14.5 dpc in the cartilage primordium, and in the developing urogenital sinus. In semiquantitative reverse transcription-polymerase chain reaction experiments, Indian hedgehog transcript was first detected in the mouse metanephros at 14.5 dpc; transcript abundance increased with gestational age, becoming maximal in adulthood. In adult kidney, Ihh transcript was detected only in the proximal convoluted tubule and proximal straight tubule.

Amino Acid Sequence↗
PubMed2006

Suppressing Wnt signaling by the hedgehog pathway through sFRP-1.

The hedgehog (Hh) signaling pathway is essential for embryonic development and carcinogenesis. Activation of Hh signaling has been identified in several types of gastrointestinal cancers, including esophageal, gastric, pancreatic, and liver cancers. Several recent studies suggest that Hh signaling activation can inhibit Wnt signaling. However, the molecular basis underlying this inhibition remains unclear. As transcription factors in the Hh signaling pathway, Gli molecules transform cells in culture, and their expression are associated with cancer development. Here we report that expression of a secreted frizzled-related protein-sFRP-1 in mouse embryonic fibroblasts is dependent on Gli1 and Gli2. In human gastric cancer cells, inhibition of Hh signaling reduces the level of sFRP-1 transcript, whereas ectopic expression of Gli1 increases the level of sFRP-1 transcript. Results from chromatin immunoprecipitation indicate that Gli1 is involved in transcriptional regulation of sFRP-1. In 293 cells with Gli1 expression, Wnt-1-mediated beta-catenin accumulation in the cytosol and DKK1 expression are all abrogated, which can be reversed by inhibiting sFRP-1 expression. Furthermore, while SIIA cells do not respond to Wnt-1-conditioned medium, inhibition of Hh signaling by smoothened (SMO) antagonist KAAD-cyclopamine (keto-N-aminoethylaminocaproyldihydrocinnamoylcyclopamine) leads to Wnt1-mediated beta-catenin accumulation in the cytosol. These data indicate that sFRP-1, a target gene of the hedgehog pathway, is involved in cross-talk between the hedgehog pathway and the Wnt pathway.

Cell Line, Transformed↗
PubMed2005

Hedgehog signaling induces cardiomyogenesis in P19 cells.

Sonic Hedgehog (Shh) is a critical signaling factor for a variety of developmental pathways during embryogenesis, including the specification of left-right asymmetry in the heart. Mice that lack Hedgehog signaling show a delay in the induction of cardiomyogenesis, as indicated by a delayed expression of Nkx2-5. To further examine a role for Shh in cardiomyogenesis, clonal populations of P19 cells that stably express Shh, termed P19(Shh) cells, were isolated. In monolayer P19(Shh) cultures the Shh pathway was functional as shown by the up-regulation of Ptc1 and Gli1 expression, but no cardiac muscle markers were activated. However, Shh expression induced cardiomyogenesis following cellular aggregation, resulting in the expression of factors expressed in cardiac muscle including GATA-4, MEF2C, and Nkx2-5. Furthermore, aggregated P19 cell lines expressing Gli2 or Meox1 also up-regulated the expression of cardiac muscle factors, leading to cardiomyogenesis. Meox1 up-regulated the expression of Gli1 and Gli2 and, thus, can modify the Shh signaling pathway. Finally, Shh, Gli2, and Meox1 all up-regulated BMP-4 expression, implying that activation of the Hedgehog pathway can regulate bone morphogenetic protein signals. Taken together, we propose a model in which Shh, functioning via Gli1/2, can specify mesodermal cells into the cardiac muscle lineage.

Actins↗
PubMed1997

Statistical modeling, phylogenetic analysis and structure prediction of a protein splicing domain common to inteins and hedgehog proteins.

Inteins, introns spliced at the protein level, and the hedgehog family of proteins involved in eucaryotic development both undergo autocatalytic proteolysis. Here, a specific and sensitive hidden Markov model (HMM) of protein splicing domain shared by inteins and the hedgehog proteins has been trained and employed for further analysis. The HMM characterizes the common features of this domain including the position where a site-specific DNA endonuclease domain is inserted in the majority of the inteins. The HMM was used to identify several new putative inteins, such as that in the Methanococcus jannaschii klbA protein, and to generate a multiple sequence alignment of sequences possessing this domain. Phylogenetic analysis suggests that hedgehog proteins evolved from inteins. Secondary and tertiary structure predictions suggest that the domain has a structure similar to a beta-sandwich. Similarities between the serine protease cleavage mechanism and the protein splicing reaction mechanism are discussed. Examination of the locations of inteins indicates that they are not inserted randomly in an extein, but are often inserted at functionally important positions in the host proteins. A specific and sensitive HMM for a domain present in klbA proteins identified several additional bacterial and archaeal family members, and analysis of the site of insertion of the intein suggests residues that may be functionally important. This domain may play a role in formation of surface-associated protein complexes.

Algorithms↗
PubMed1998

Transducing Hedgehog: the story so far.

The secreted proteins of the Hedgehog family have been implicated in many different processes in vertebrate development including cartilage differentiation, myotome and sclerotome specification, hair follicle development, limb morphogenesis and the specification of different neuronal cell types. In addition, the aberrant activation of the Hedgehog pathway has been identified as the likely cause of a number of tumours in humans including basal cell carcinomas (BCCs) and primitive neurectodermal tumours (PNETs). Elucidating the mechanisms by which Hedgehog signals are transduced will thus have widespread implications for our understanding of both normal development and disease.

Animals↗
PubMed2005

Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: an animal model of holoprosencephaly.

The pathogenesis of holoprosencephaly is multifactorial, and blockage of Sonic hedgehog signaling is one of the most important causative factors in animal models and human cases. In this study, the authors analyzed facial anomalies of mouse embryos, which were cultured in vitro and exposed to cyclopamine, an alkaloid blocker of Sonic hedgehog signaling. When cultured with cyclopamine for embryonic day 8.5 to 10.5, the whole body size was smaller than normal, and the distance and angle between the nasal placodes were remarkably reduced. Extension of the cranial surface vessels also was noted. No cyclopia was observed. Migration of the cranial neural crest cells seemed to be intact. Expressions of Patched-1 and Gli-1, downstream genes of Sonic hedgehog signaling, also were down-regulated in in situ hybridization and real-time reverse transcriptase-polymerase chain reaction analyses. The authors consider that these facial anomalies represent milder phenotypes of holoprosencephaly.

Animals↗
PubMed2006

The chicken talpid3 gene encodes a novel protein essential for Hedgehog signaling.

Talpid3 is a classical chicken mutant with abnormal limb patterning and malformations in other regions of the embryo known to depend on Hedgehog signaling. We combined the ease of manipulating chicken embryos with emerging knowledge of the chicken genome to reveal directly the basis of defective Hedgehog signal transduction in talpid3 embryos and to identify the talpid3 gene. We show in several regions of the embryo that the talpid3 phenotype is completely ligand independent and demonstrate for the first time that talpid3 is absolutely required for the function of both Gli repressor and activator in the intracellular Hedgehog pathway. We map the talpid3 locus to chromosome 5 and find a frameshift mutation in a KIAA0586 ortholog (ENSGALG00000012025), a gene not previously attributed with any known function. We show a direct causal link between KIAA0586 and the mutant phenotype by rescue experiments. KIAA0586 encodes a novel protein, apparently specific to vertebrates, that localizes to the cytoplasm. We show that Gli3 processing is abnormal in talpid3 mutant cells but that Gli3 can still translocate to the nucleus. These results suggest that the talpid3 protein operates in the cytoplasm to regulate the activity of both Gli repressor and activator proteins.

Amino Acid Sequence↗
PubMedDate not supplied

Correlative study of the ultrastructure and the physiology of the seasonal regression of the epididymal epithelium in the hedgehog Paraechinus micropus.

The seasonal variations in the ultrastructure and physiology of the epididymis of hedgehog were studied in relation to the reproductive functions. Five adult male hedgehogs were sacrificed every alternate month for one calendar year and the epididymis was fixed in Bouin's, Zenker and formol-calcium for light microscopy and in cold buffered glutaraldehyde, post-fixed in osmium tetraoxide for electron microscopy. The epididymal epithelium consists of four types of cells, the principal, the apical, the dark and the basal cells. The principal cells like other steroid synthesizing cells, contain the extensive Golgi apparatus, the smooth and the rough endoplasmic reticulum (SER and RER), the secretory vesicles and the lipid granules during the breeding season, but they are practically devoid of these cell organelles during regression, except for the retarded Golgi and moderate RER. The basal cell, on the other hand, show lipids and well developed organelles during regression but poorly developed structure in the sexually active hedgehog and possibly function as the cells storing lipids during regression and which are subsequently used at the beginning of the recrudescence. The epididymal epithelium recrudesces along with the seminiferous epithelium prior to the spermatozoa reaching the epididymal lumen, whereas the accessory sex glands which are also the extratesticular androgen dependent organs, still show regressed structure. Thus, the ultrastructural and the physiological observations suggest that the principal cells are probably the site of androgen synthesis and they become fully developed along with the cells in the testis on stimulation from the pituitary at the beginning of the recrudescence.

Animals↗
PubMed1994

Reciprocal connections of the motor neocortical area with the contralateral thalamus in the hedgehog (Erinaceus europaeus) brain.

Horseradish peroxidase unilateral injections in various neocortical areas (prefrontal, somatosensory, auditory, visual) of the hedgehog (Erinaceus europaeus) brain resulted in labelling of nuclei in the ipsilateral thalamus known from studies in other species and in the hedgehog to project to these areas. However, injections in the motor area resulted in retrograde and anterograde labelling of nuclei in both the ipsilateral and contralateral thalamus. These nuclei included the ventral lateral nucleus (VL), the intralaminar nuclei (ILN), the mediodorsal nucleus (MD) and midline nuclei. Large unilateral injections located mainly laterally in the thalamus labelled cells, contralaterally, in the ventral lateral geniculate nucleus, the intergeniculate leaflet and the reticular nucleus of the thalamus, but never in VL, ILN and MD. The present results confirm previously described bilateral thalamocortical projections from the VL to the somatosensorimotor area in this species (Regidor and Divac, Brain Behav. Evol., 39, 265-269, 1992) and in addition demonstrate that (i) bilateral thalamocortical projections are established preferentially with the motor area, (ii) several nuclei are involved in such connections, (iii) these connections are reciprocal and topographically organized, and (iv) labelling in the contralateral thalamus observed in the present study is not a result of transneuronal transport of the tracer through thalamothalamic connections. This organization is unique among mammals and supports previous anatomical and electrophysiological findings, on the basis of which it has been suggested that the hedgehog retains a primitive character in neocortical and thalamic evolution.

Animals↗
PubMed1991

Pineal melatonin concentrations during day and night in the adult hedgehog: effect of a light pulse at night and superior cervical ganglionectomy.

The European hedgehog (Erinaceus europaeus L.) is a hibernating mammal and seasonal breeder in which numerous circadian and circannual rhythms are entrained and synchronized by photoperiod. The present study was undertaken in order to establish the involvement of the pineal gland in transducing the photoperiodic message in this species. Pineal melatonin concentrations were determined by radioimmunoassay in female hedgehogs kept under natural climatic conditions and killed during the light:dark (L:D) cycle in spring and autumn, after the interruption of darkness by a 45 min light pulse, and after bilateral superior cervical ganglionectomy (SCGx). Absolute melatonin concentrations were low (less than 100 pg/pineal) in the pineal gland. Under natural climatic conditions, in spring and in autumn, pineal melatonin concentrations exhibited a marked diurnal rhythmicity, with very low levels in the day (1200: less than 10 pg/pineal) and high levels during the night (2200: 71.9 +/- 18.6 pg/pineal; 0200: 42.5 +/- 15.6 pg/pineal). The 45 min light pulse during darkness depressed rapidly and significantly the melatonin content (dark + light [D + L]: less than 10 pg/pineal), but a subsequent return to darkness restored high melatonin content after approximately 2 h (D + L + D: 65.4 +/- 20.2 pg/pineal). After bilateral SCGx, melatonin concentrations were reduced and no increase during night could be observed, either in animals sacrificed 42 days after SCGx or in animals killed 2 years after SCGx. In the hedgehog, as in other mammals, pineal melatonin concentrations are related to the light:dark cycle. Such data indicate that during the year, in this species, the effects of light on seasonal endocrine rhythms may be mediated by the pineal gland.

Animals↗
PubMed2004

Acinic cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

A male African pygmy hedgehog (Atelerix albiventris), estimated to be 3 years old, presented with exophthalmos and fixed abduction of the right eye. Radiographic examination revealed a retrobulbar tumor in the right orbital cavity. The mass was surgically resected but recurred 3 months later and the hedgehog died. There was no gross or microscopic evidence of salivary or lacrimal gland involvement of the tumor at surgery or at necropsy. The histopathologic, immunohistochemical, and ultrastructural findings were those of acinic cell carcinoma, the origin of which was unknown. This is the first known case of acinic cell carcinoma in an African hedgehog.

Animals↗
PubMed2006

The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling.

Bone morphogenetic protein 2 (BMP-2) plays a critical role in osteoblast function. In Drosophila, Cubitus interruptus (Ci), which mediates hedgehog signaling, regulates gene expression of dpp, the ortholog of mammalian BMP-2. Null mutation of the transcription factor Gli2, a mammalian homolog of Ci, results in severe skeletal abnormalities in mice. We hypothesize that Gli2 regulates BMP-2 gene transcription and thus osteoblast differentiation. In the present study, we show that overexpression of Gli2 enhances BMP-2 promoter activity and mRNA expression in osteoblast precursor cells. In contrast, knocking down Gli2 expression by Gli2 small interfering RNA or genetic ablation of the Gli2 gene results in significant inhibition of BMP-2 gene expression in osteoblasts. Promoter analyses, including chromatin immunoprecipitation and electrophoretic mobility shift assays, provided direct evidence that Gli2 physically interacts with the BMP-2 promoter. Functional studies showed that Gli2 is required for osteoblast maturation in a BMP-2-dependent manner. Finally, Sonic hedgehog (Shh) stimulates BMP-2 promoter activity and osteoblast differentiation, and the effects of Shh are mediated by Gli2. Taken together, these results indicate that Gli2 mediates hedgehog signaling in osteoblasts and is a powerful activator of BMP-2 gene expression, which is required in turn for normal osteoblast differentiation.

Animals↗
PubMed2002

Normal haematological values of European hedgehogs (Erinaceus europaeus) from an English rehabilitation centre.

Blood samples were taken from 29 male and 21 female clinically normal European hedgehogs (Erinaceus europaeus) that had been overwintered in an English rehabilitation centre, and the mean (sd) and ranges of their haematological values were determined. The mean cellular volume and lymphocyte counts of the female hedgehogs were slightly but significantly higher than those of the male hedgehogs.

Animals↗
PubMed2006

The hedgehog pathway and neurological disorders.

The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system, this dual ability is especially important in regulating the behavior of neural stem and progenitor cells. This review summarizes information connecting hedgehog signaling and neural diseases, including neurodegenerative disorders and brain tumors, particularly medulloblastoma. We also describe the discovery and utility of small molecule agonists and antagonists of this pathway and their potential as novel types of therapeutics.

Animals↗
PubMed1992

Auditory cortex of the long-eared hedgehog (Hemiechinus auritus): II. Tuning properties.

The forebrain of hedgehogs is considered by many investigators as one of the simplest and most primitive among extant placental mammals. In a recent study we have shown that the auditory cortex of the long-eared hedgehog (Hemiechinus auritus) comprises two distinct auditory fields, which are tonotopically organized. In this study, we describe tuning properties of single cells in these two fields. Application of the Q10dB and Square Root measures for determining sharpness of tuning revealed that, although most of the cells in the more anterior field, which is considered primary, are sharply tuned, on the average they are more broadly tuned than cells in the primary auditory cortex of other mammals. In the posterior field, the distribution of narrowly and broadly tuned cells is equal. Narrowly tuned cells in both fields are equally narrow, as are the broadly tuned cells. Latencies of single cells in both fields are frequency and intensity dependent and are somewhat longer than these found in other mammals. The distribution of BFs vs. threshold intensity matches fairly well the behavioral audiogram previously described. Our findings suggest that, in spite of the view that the isocortex of hedgehogs represents a 'primitive' condition, some basic tuning properties of their auditory cortex cells are comparable to those of other mammals.

Animals↗
PubMed1975

Sustained fertility in a non-scrotal mammal, the Indian hedgehog (Hemiechinus auritus Collaris), after CdCl2 administration.

The effects of a single subcutaneous injection of CdCl2 (0.04 mmol/kg body weight) were studied on the testes and caput epididymidis of a non-scrotal mammal, Hemiechinus auritus, and scrotal laboratory mouse. The histological structure of the testes and caput epididymidis of the hedgehog remains normal after 21 days of CdCl2 injection. Testes and sex accessory glands did not show any significant change in weight. The testes and sex accessory organs of mice under comparable condition showed weight loss and involution in tubule diameter. A temperature differential of 1 degree C was found to exist between the rectum and the cremaster sac of the hedgehog. This small temperature difference and the absence of a counter-current mechanism may be involved in conferring the CdCl2 resistance to the testes and epididymis of the hedgehog.

Animals↗
PubMed2003

Expression of hedgehog proteins in the human thymus.

The Hedgehog (Hh) family of secreted proteins includes intercellular signaling molecules that specify cell fate and patterning during the development of many tissues. In this study we show that the different components of the Hh signaling pathway are expressed in human thymus. The three mammalian Hh proteins, Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog, are produced by thymic epithelial cells. Shh-expressing epithelial cells are restricted to the thymic subcapsula and medulla, whereas Ihh- and Dhh-producing epithelial cells are distributed throughout the thymus. The requisite Hh receptors, Patched 1(Ptc1) and Smoothened (Smo), and the Gli transcription factors are expressed by thymocytes and also by epithelial cells. Ptc1 is expressed in most thymocyte subsets, whereas Smo expression is mainly associated with immature thymocytes. The isoform of the Ptc receptor, Ptc2, is expressed only by intrathymic progenitor cells and epithelial cells. Other Hh-binding proteins with modulating functions, such as Hedgehog-interacting protein (Hip) and growth arrest-specific gene-1 (Gas-1), are also expressed in human thymus. Our study shows that the intrathymic expression pattern of the Hh signaling pathway components is complex and suggests that Hh proteins may regulate human thymocyte differentiation from the earliest developmental stages, as well as thymic epithelial cell function.

Cell Line↗