Shh

Summary

Gene Symbol: Shh
Description: sonic hedgehog
Alias: ShhNC, sonic hedgehog protein, shh unprocessed N-terminal signaling and C-terminal autoprocessing domains, sonic hedgehog homolog
Species: rat
Products:     Shh

Top Publications

  1. Mastronardi F, daCruz L, Wang H, Boggs J, Moscarello M. The amount of sonic hedgehog in multiple sclerosis white matter is decreased and cleavage to the signaling peptide is deficient. Mult Scler. 2003;9:362-71 pubmed
    We have demonstrated that sonic hedgehog (Shh), vital for oligodendrocyte development, is present in both gray and white matter of normal human brain...
  2. Outram S, Varas A, Pepicelli C, Crompton T. Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte. Immunity. 2000;13:187-97 pubmed
    ..The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development...
  3. Haraguchi R, Mo R, Hui C, Motoyama J, Makino S, Shiroishi T, et al. Unique functions of Sonic hedgehog signaling during external genitalia development. Development. 2001;128:4241-50 pubmed
    ..The sonic hedgehog (Shh) gene and its signaling genes have been found to be dynamically expressed during murine external genitalia ..
  4. Sagai T, Hosoya M, Mizushina Y, Tamura M, Shiroishi T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development. 2005;132:797-803 pubmed
    ..in a conserved non-coding region in intron 5 of the Lmbr1 locus, which is 1 Mb away from the sonic hedgehog (Shh) coding sequence, are responsible for mouse and human preaxial polydactyly with mirror-image digit duplications...
  5. Shah D, Hager Theodorides A, Outram S, Ross S, Varas A, Crompton T. Reduced thymocyte development in sonic hedgehog knockout embryos. J Immunol. 2004;172:2296-306 pubmed
    ..In this study we provide genetic evidence that Sonic Hedgehog (Shh) has a role in the control of murine T cell development...
  6. Lai K, Kaspar B, Gage F, Schaffer D. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci. 2003;6:21-7 pubmed
    ..Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells...
  7. Rajendran R, Jha S, Fernandes K, Banerjee S, Mohammad F, Dias B, et al. Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus. Neurosci Lett. 2009;453:190-4 pubmed publisher
    ..Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-..
  8. Kruger M, Mennerich D, Fees S, Schafer R, Mundlos S, Braun T. Sonic hedgehog is a survival factor for hypaxial muscles during mouse development. Development. 2001;128:743-52 pubmed
    Sonic hedgehog (Shh) has been proposed to function as an inductive and trophic signal that controls development of epaxial musculature in vertebrate embryos...
  9. Stone D, Hynes M, Armanini M, Swanson T, Gu Q, Johnson R, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384:129-34 pubmed
    The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development...
  10. Dai R, Zhu S, Xia Y, Mao L, Mei Y, Yao Y, et al. Sonic hedgehog protects cortical neurons against oxidative stress. Neurochem Res. 2011;36:67-75 pubmed publisher
    ..Recent studies have indicated that the sonic hedgehog (SHH) signaling pathway is involved in these diseases, but the underlying mechanisms remains elusive...

Detail Information

Publications62

  1. Mastronardi F, daCruz L, Wang H, Boggs J, Moscarello M. The amount of sonic hedgehog in multiple sclerosis white matter is decreased and cleavage to the signaling peptide is deficient. Mult Scler. 2003;9:362-71 pubmed
    We have demonstrated that sonic hedgehog (Shh), vital for oligodendrocyte development, is present in both gray and white matter of normal human brain...
  2. Outram S, Varas A, Pepicelli C, Crompton T. Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte. Immunity. 2000;13:187-97 pubmed
    ..The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development...
  3. Haraguchi R, Mo R, Hui C, Motoyama J, Makino S, Shiroishi T, et al. Unique functions of Sonic hedgehog signaling during external genitalia development. Development. 2001;128:4241-50 pubmed
    ..The sonic hedgehog (Shh) gene and its signaling genes have been found to be dynamically expressed during murine external genitalia ..
  4. Sagai T, Hosoya M, Mizushina Y, Tamura M, Shiroishi T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development. 2005;132:797-803 pubmed
    ..in a conserved non-coding region in intron 5 of the Lmbr1 locus, which is 1 Mb away from the sonic hedgehog (Shh) coding sequence, are responsible for mouse and human preaxial polydactyly with mirror-image digit duplications...
  5. Shah D, Hager Theodorides A, Outram S, Ross S, Varas A, Crompton T. Reduced thymocyte development in sonic hedgehog knockout embryos. J Immunol. 2004;172:2296-306 pubmed
    ..In this study we provide genetic evidence that Sonic Hedgehog (Shh) has a role in the control of murine T cell development...
  6. Lai K, Kaspar B, Gage F, Schaffer D. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci. 2003;6:21-7 pubmed
    ..Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells...
  7. Rajendran R, Jha S, Fernandes K, Banerjee S, Mohammad F, Dias B, et al. Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus. Neurosci Lett. 2009;453:190-4 pubmed publisher
    ..Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-..
  8. Kruger M, Mennerich D, Fees S, Schafer R, Mundlos S, Braun T. Sonic hedgehog is a survival factor for hypaxial muscles during mouse development. Development. 2001;128:743-52 pubmed
    Sonic hedgehog (Shh) has been proposed to function as an inductive and trophic signal that controls development of epaxial musculature in vertebrate embryos...
  9. Stone D, Hynes M, Armanini M, Swanson T, Gu Q, Johnson R, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384:129-34 pubmed
    The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development...
  10. Dai R, Zhu S, Xia Y, Mao L, Mei Y, Yao Y, et al. Sonic hedgehog protects cortical neurons against oxidative stress. Neurochem Res. 2011;36:67-75 pubmed publisher
    ..Recent studies have indicated that the sonic hedgehog (SHH) signaling pathway is involved in these diseases, but the underlying mechanisms remains elusive...
  11. Sharpe J, Lettice L, Hecksher Sorensen J, Fox M, Hill R, Krumlauf R. Identification of sonic hedgehog as a candidate gene responsible for the polydactylous mouse mutant Sasquatch. Curr Biol. 1999;9:97-100 pubmed
    ..of the anterior limb bud resulting in ectopic expression of signalling components such as Sonic hedgehog (Shh) and fibroblast growth factor-4 (Fgf4), but little is known about the molecular causes of this misregulation...
  12. Lewis P, Gritli Linde A, Smeyne R, Kottmann A, McMahon A. Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol. 2004;270:393-410 pubmed
    The signals that promote regional growth and development of the brain are not well understood. Sonic hedgehog (Shh) is produced by Purkinje cells of the cerebellum and is a potent inducer of granule cell proliferation...
  13. Vokes S, Ji H, McCuine S, Tenzen T, Giles S, Zhong S, et al. Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development. 2007;134:1977-89 pubmed
    Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network...
  14. Wechsler Reya R, Scott M. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron. 1999;22:103-14 pubmed
    ..We show that Sonic hedgehog (Shh), which is made by Purkinje cells, regulates the division of granule cell precursors (GCPs)...
  15. Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell. 2001;106:781-92 pubmed
    ..We show that Smo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse embryo...
  16. Wang Y, Imitola J, Rasmussen S, O Connor K, Khoury S. Paradoxical dysregulation of the neural stem cell pathway sonic hedgehog-Gli1 in autoimmune encephalomyelitis and multiple sclerosis. Ann Neurol. 2008;64:417-27 pubmed publisher
    ..We investigated the sonic hedgehog (Shh)-Gli1 pathway, an important signaling pathway for NSCs, in experimental autoimmune encephalomyelitis (EAE) and ..
  17. Wijgerde M, McMahon J, Rule M, McMahon A. A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev. 2002;16:2849-64 pubmed
    ..Surprisingly, in the absence of Sonic hedgehog (Shh), we observe the presence of a Smo-dependent Hh signaling activity operating in the ventral half of the spinal cord ..
  18. Bond C, Angeloni N, Harrington D, Stupp S, Podlasek C. Sonic Hedgehog regulates brain-derived neurotrophic factor in normal and regenerating cavernous nerves. J Sex Med. 2013;10:730-7 pubmed publisher
    ..Sonic hedgehog (SHH) treatment promotes CN regeneration. The mechanism of how this occurs is unknown...
  19. Liu A, Wang B, Niswander L. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development. 2005;132:3103-11 pubmed
    ..Sonic hedgehog (Shh) expression is normal, yet Ptch1 and Gli1, two known targets of Hh signaling, are greatly reduced, consistent with ..
  20. Chiang C, Litingtung Y, Harris M, Simandl B, Li Y, Beachy P, et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol. 2001;236:421-35 pubmed
    The secreted protein encoded by the Sonic hedgehog (Shh) gene is localized to the posterior margin of vertebrate limb buds and is thought to be a key signal in establishing anterior-posterior limb polarity...
  21. Pan Y, Bai C, Joyner A, Wang B. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol. 2006;26:3365-77 pubmed
    Gli2 and Gli3 are the primary transcription factors that mediate Sonic hedgehog (Shh) signals in the mouse. Gli3 mainly acts as a transcriptional repressor, because the majority of full-length Gli3 protein is proteolytically processed...
  22. Fan C, Lee C, Tessier Lavigne M. A role for WNT proteins in induction of dermomyotome. Dev Biol. 1997;191:160-5 pubmed
    ....
  23. Charytoniuk D, Traiffort E, Hantraye P, Hermel J, Galdes A, Ruat M. Intrastriatal sonic hedgehog injection increases Patched transcript levels in the adult rat subventricular zone. Eur J Neurosci. 2002;16:2351-7 pubmed
    The morphogen sonic hedgehog (Shh) is implicated in neural tissue patterning and the growth of brain structures during embryogenesis and postnatal development and is also present in the adult brain...
  24. Mo R, Kim J, Zhang J, Chiang C, Hui C, Kim P. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol. 2001;159:765-74 pubmed
    ..Sonic hedgehog (Shh) is an endoderm-derived signaling molecule that induces mesodermal gene expression in the chick hindgut...
  25. Ramalho Santos M, Melton D, McMahon A. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000;127:2763-72 pubmed
    ..These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations. ..
  26. Nery S, Wichterle H, Fishell G. Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development. 2001;128:527-40 pubmed
    This study addresses the role of Sonic hedgehog (Shh) in promoting the generation of oligodendrocytes in the mouse telencephalon...
  27. Hwang J, Weng Y, Lin J, Bau D, Ko F, Tsai F, et al. Hypoxia-induced compensatory effect as related to Shh and HIF-1alpha in ischemia embryo rat heart. Mol Cell Biochem. 2008;311:179-87 pubmed publisher
    ..increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1alpha and Shh. The relationship between HIF-1alpha and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh ..
  28. Allen B, Tenzen T, McMahon A. The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev. 2007;21:1244-57 pubmed
    ..Transcriptional profiling identified Growth-arrest-specific 1 (Gas1) as a general negative target of Shh signaling. Data presented here define Gas1 as a novel positive component of the Shh signaling cascade...
  29. Al Ayadhi L. Relationship between Sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders. Neurochem Res. 2012;37:394-400 pubmed publisher
    ..We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD...
  30. Madhavan L, Daley B, Davidson B, Boudreau R, Lipton J, Cole Strauss A, et al. Sonic Hedgehog Controls the Phenotypic Fate and Therapeutic Efficacy of Grafted Neural Precursor Cells in a Model of Nigrostriatal Neurodegeneration. PLoS ONE. 2015;10:e0137136 pubmed publisher
    ..the roles of two donor NPC molecules, namely glial cell-line derived neurotrophic factor (GDNF) and sonic hedgehog (SHH), in the protection of substantia nigra dopamine neurons in rats treated with 6-hydroxydopamine (6-OHDA)...
  31. Fang M, Lu Y, Chen G, Shen L, Pan Y, Wang X. Increased expression of sonic hedgehog in temporal lobe epileptic foci in humans and experimental rats. Neuroscience. 2011;182:62-70 pubmed publisher
    Sonic hedgehog (Shh) is a soluble signaling protein that is crucial in regulating cell proliferation, migration and differentiation, axonal guidance and neural progenitor cell survival during nervous system development...
  32. Sasaki Y, O Kane S, Dixon J, Dixon M, Ferguson M. Temporal and spatial expression of Pax9 and Sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos. Arch Oral Biol. 2007;52:260-7 pubmed
    Transforming growth factor-beta (TGF-beta3) gene disruption causes cleft secondary palate. Pax9 and Sonic hedgehog (Shh) genes are involved in the patterning of vertebrate embryonic tissues, including the facial skeleton...
  33. Buttitta L, Mo R, Hui C, Fan C. Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction. Development. 2003;130:6233-43 pubmed
    Sonic hedgehog (Shh) signaling is essential for sclerotome development in the mouse...
  34. Charron F, Stein E, Jeong J, McMahon A, Tessier Lavigne M. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 2003;113:11-23 pubmed
    ..We show that the morphogen Sonic hedgehog (Shh) can mimic the additional chemoattractant activity of the floor plate in vitro and can act directly as a ..
  35. Tsukui T, Capdevila J, Tamura K, Ruiz Lozano P, Rodriguez Esteban C, Yonei Tamura S, et al. Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proc Natl Acad Sci U S A. 1999;96:11376-81 pubmed
    Asymmetric expression of Sonic hedgehog (Shh) in Hensen's node of the chicken embryo plays a key role in the genetic cascade that controls left-right asymmetry, but its involvement in left-right specification in other vertebrates remains ..
  36. Unger S, Copland I, Tibboel D, Post M. Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia. Am J Pathol. 2003;162:547-55 pubmed
    ..The sonic hedgehog (Shh) cascade is crucial for the patterning of the early respiratory system in mice...
  37. Gao H, Zhang Z, Jiang Z, Wang D, Huang Y, Wang W. [Mutation and expression of WNT8b gene and SHH gene in Hirschsprung disease]. Zhonghua Wei Chang Wai Ke Za Zhi. 2010;13:758-61 pubmed
    To investigate the relationship of WNT8b and SHH genes mutation and Hirschsprung disease(HSCR) in Chinese children. Preoperative whole blood preparations in 72 children with sporadic HSCR from northeast China were collected(study group)...
  38. Mahlapuu M, Enerback S, Carlsson P. Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development. 2001;128:2397-406 pubmed
    ..Similar malformations are observed in mutants that are defective in the sonic hedgehog (Shh) signaling pathway, and we show that exogenous Shh activates transcription of Foxf1 in developing lung...
  39. Pringle N, Yu W, Guthrie S, Roelink H, Lumsden A, Peterson A, et al. Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Dev Biol. 1996;177:30-42 pubmed
    ..tube only when they were cocultured with fragments of notochord or in the presence of purified Sonic hedgehog (Shh) protein...
  40. Bond C, Tang Y, Podlasek C. Neural influences on sonic hedgehog and apoptosis in the rat penis. Biol Reprod. 2008;78:947-56 pubmed publisher
    The role of sonic hedgehog (SHH) in maintaining corpora cavernosal morphology in the adult penis has been established; however, the mechanism of how SHH itself is regulated remains unclear...
  41. Sussman C, Davies J, Miller R. Extracellular and intracellular regulation of oligodendrocyte development: roles of Sonic hedgehog and expression of E proteins. Glia. 2002;40:55-64 pubmed
    ..The signaling molecule Sonic hedgehog (Shh) is critical for normal development of oligodendrocytes, although the precise influences of Shh on cells of the ..
  42. Lee C, Buttitta L, May N, Kispert A, Fan C. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development. 2000;127:109-18 pubmed
    ..Noggin and SHH-N have been implicated as the ventralizing signals produced by the notochord...
  43. Albuisson J, Isidor B, Giraud M, Pichon O, Marsaud T, David A, et al. Identification of two novel mutations in Shh long-range regulator associated with familial pre-axial polydactyly. Clin Genet. 2011;79:371-7 pubmed publisher
    ..MIM #186200) are a group of closely related conditions caused by mutations in a long-range Sonic hedgehog (SHH, MIM *600725) regulator called ZRS...
  44. Patterson V, Damrau C, Paudyal A, Reeve B, Grimes D, Stewart M, et al. Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway. Hum Mol Genet. 2009;18:1719-39 pubmed publisher
    The mammalian Sonic hedgehog (Shh) signalling pathway is essential for embryonic development and the patterning of multiple organs...
  45. Yang L, Wang Y, Mao H, Fleig S, Omenetti A, Brown K, et al. Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells. J Hepatol. 2008;48:98-106 pubmed
    ..This study evaluates the hypothesis that autocrine production of Sonic hedgehog (Shh) promotes MFB growth...
  46. Gold D, Baek S, Schork N, Rose D, Larsen D, Sachs B, et al. RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways. Neuron. 2003;40:1119-31 pubmed
    ....
  47. Garg V, Yamagishi C, Hu T, Kathiriya I, Yamagishi H, Srivastava D. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Dev Biol. 2001;235:62-73 pubmed
    ..Sonic hedgehog (Shh) is also expressed in the pharyngeal arches and is necessary for normal craniofacial development...
  48. Moore Scott B, Manley N. Differential expression of Sonic hedgehog along the anterior-posterior axis regulates patterning of pharyngeal pouch endoderm and pharyngeal endoderm-derived organs. Dev Biol. 2005;278:323-35 pubmed
    Previous studies have implicated Sonic hedgehog (Shh) as an important regulator of pharyngeal region development. Here we show that Shh is differentially expressed within the pharyngeal endoderm along the anterior-posterior axis...
  49. Levine E, Roelink H, Turner J, Reh T. Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J Neurosci. 1997;17:6277-88 pubmed
    ..N-terminal recombinant Sonic Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the numbers of retinal cells of various ..
  50. Rice R, Spencer Dene B, Connor E, Gritli Linde A, McMahon A, Dickson C, et al. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. J Clin Invest. 2004;113:1692-700 pubmed
    ..Using Fgf10-/-, FGF receptor 2b-/- (Fgfr2b-/-), and Sonic hedgehog (Shh) mutant mice, which all exhibit cleft palate, we show that Shh is a downstream target of Fgf10/Fgfr2b signaling...