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Gene Ontology Classifications
sonic hedgehog

Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Shh. (This text reflects annotations as of Tuesday, May 26, 2015.)
Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
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  24. Corrales JD et al. (2004) Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development. Development, 131:5581-90. (PubMed:15496441)
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  28. Dakubo GD et al. (2003) Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development. Development, 130:2967-80. (PubMed:12756179)
  29. Dassule HR et al. (2000) Sonic hedgehog regulates growth and morphogenesis of the tooth Development, 127:4775-85. (PubMed:11044393)
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  32. Fernandez-L A et al. (2009) YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev, 23:2729-41. (PubMed:19952108)
  33. Fu M et al. (2004) Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut. J Cell Biol, 166:673-84. (PubMed:15337776)
  34. Fuse N et al. (1999) Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for patched. Proc Natl Acad Sci U S A, 96:10992-9. (PubMed:10500113)
  35. Gao N et al. (2005) Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation. Development, 132:3431-43. (PubMed:15987773)
  36. Garg V et al. (2001) Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Dev Biol, 235:62-73. (PubMed:11412027)
  37. Gold DA et al. (2003) RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways. Neuron, 40:1119-31. (PubMed:14687547)
  38. Gritli-Linde A et al. (2001) The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. Dev Biol, 236:364-86. (PubMed:11476578)
  39. Grobe K et al. (2005) Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function. Development, 132:3777-86. (PubMed:16020517)
  40. Haraguchi R et al. (2001) Unique functions of Sonic hedgehog signaling during external genitalia development. Development, 128:4241-50. (PubMed:11684660)
  41. Harfe BD et al. (2004) Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell, 118:517-28. (PubMed:15315763)
  42. Hashizume A et al. (2006) Hedgehog peptide promotes cell polarization and lumen formation in developing mouse submandibular gland. Biochem Biophys Res Commun, 339:996-1000. (PubMed:16332353)
  43. Hebrok M et al. (2000) Regulation of pancreas development by hedgehog signaling. Development, 127:4905-13. (PubMed:11044404)
  44. Hu MC et al. (2006) GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development, 133:569-78. (PubMed:16396903)
  45. Iwatsuki K et al. (2007) Wnt signaling interacts with Shh to regulate taste papilla development. Proc Natl Acad Sci U S A, 104:2253-8. (PubMed:17284610)
  46. Izraeli S et al. (1999) The SIL gene is required for mouse embryonic axial development and left-right specification. Nature, 399:691-4. (PubMed:10385121)
  47. Jaskoll T et al. (2004) Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis. Dev Dyn, 229:722-32. (PubMed:15042696)
  48. Jeong J et al. (2005) Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1. Development, 132:143-54. (PubMed:15576403)
  49. Karlsson L et al. (1999) Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle. Development, 126:2611-21. (PubMed:10331973)
  50. Kim JW et al. (2006) Hedgehog-regulated localization of Vax2 controls eye development. Genes Dev, 20:2833-47. (PubMed:17043310)
  51. Kim PC et al. (2001) Murine models of VACTERL syndrome: Role of sonic hedgehog signaling pathway. J Pediatr Surg, 36:381-4. (PubMed:11172440)
  52. Kittappa R et al. (2007) The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol, 5:e325. (PubMed:18076286)
  53. Kraus P et al. (2001) Some distal limb structures develop in mice lacking Sonic hedgehog signaling. Mech Dev, 100:45-58. (PubMed:11118883)
  54. Kruger M et al. (2001) Sonic hedgehog is a survival factor for hypaxial muscles during mouse development. Development, 128:743-52. (PubMed:11171399)
  55. Lallemand Y et al. (2009) Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb. Dev Biol, 331:189-98. (PubMed:19422820)
  56. Lamm ML et al. (2002) Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Dev Biol, 249:349-66. (PubMed:12221011)
  57. Lan Y et al. (2009) Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development, 136:1387-96. (PubMed:19304890)
  58. Lavine KJ et al. (2006) Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes Dev, 20:1651-66. (PubMed:16778080)
  59. Lewis PM et al. (2004) Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol, 270:393-410. (PubMed:15183722)
  60. Lewis PM et al. (2001) Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell, 105:599-612. (PubMed:11389830)
  61. Li X et al. (2004) Hedgehog can drive terminal differentiation of amniote slow skeletal muscle. BMC Dev Biol, 4:9. (PubMed:15238161)
  62. Li Y et al. (2004) Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis. Dev Biol, 270:214-31. (PubMed:15136151)
  63. Litingtung Y et al. (1998) Sonic hedgehog is essential to foregut development [see comments] Nat Genet, 20:58-61. (PubMed:9731532)
  64. Liu A et al. (2005) Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development, 132:3103-11. (PubMed:15930098)
  65. Mahlapuu M et al. (2001) Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development, 128:2397-406. (PubMed:11493558)
  66. Martinelli DC et al. (2007) Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes Dev, 21:1231-43. (PubMed:17504940)
  67. Martinelli DC et al. (2009) A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1. J Biol Chem, 284:19169-72. (PubMed:19478089)
  68. McMahon JA et al. (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev, 12:1438-52. (PubMed:9585504)
  69. Meyers EN et al. (1999) Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH. Science, 285:403-6. (PubMed:10411502)
  70. Michno K et al. (2003) Shh expression is required for embryonic hair follicle but not mammary gland development. Dev Biol, 264:153-65. (PubMed:14623238)
  71. Mill P et al. (2005) Shh controls epithelial proliferation via independent pathways that converge on N-Myc. Dev Cell, 9:293-303. (PubMed:16054035)
  72. Miller LA et al. (2001) Immunolocalization of sonic hedgehog (Shh) in developing mouse lung. J Histochem Cytochem, 49:1593-604. (PubMed:11724907)
  73. Miller LA et al. (2004) Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung. Dev Dyn, 231:57-71. (PubMed:15305287)
  74. Mo R et al. (2001) Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol, 159:765-74. (PubMed:11485934)
  75. Moore-Scott BA et al. (2005) Differential expression of Sonic hedgehog along the anterior-posterior axis regulates patterning of pharyngeal pouch endoderm and pharyngeal endoderm-derived organs. Dev Biol, 278:323-35. (PubMed:15680353)
  76. Nasr R et al. (2008) Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med, 14:1333-42. (PubMed:19029980)
  77. Nery S et al. (2001) Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development, 128:527-40. (PubMed:11171336)
  78. Ocbina PJ et al. (2011) Complex interactions between genes controlling trafficking in primary cilia. Nat Genet, 43:547-53. (PubMed:21552265)
  79. Oh S et al. (2005) Specific requirements of sonic hedgehog signaling during oligodendrocyte development. Dev Dyn, 234:489-96. (PubMed:15880651)
  80. Okada A et al. (2006) Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature, 444:369-73. (PubMed:17086203)
  81. Outram SV et al. (2009) Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation. Blood, 113:2217-28. (PubMed:19109233)
  82. Outram SV et al. (2000) Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte. Immunity, 13:187-97. (PubMed:10981962)
  83. Pan Y et al. (2006) Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol, 26:3365-77. (PubMed:16611981)
  84. Pan Y et al. (2009) Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development. Dev Biol, 326:177-89. (PubMed:19056373)
  85. Patterson VL et al. (2009) 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, 18:1719-39. (PubMed:19223390)
  86. Pepicelli CV et al. (1998) Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol, 8:1083-6. (PubMed:9768363)
  87. Podlasek CA et al. (1999) Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium. Dev Biol, 209:28-39. (PubMed:10208740)
  88. Pringle NP et al. (1996) Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Dev Biol, 177:30-42. (PubMed:8660874)
  89. Qin J et al. (2011) Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components. Proc Natl Acad Sci U S A, 108:1456-61. (PubMed:21209331)
  90. Ramalho-Santos M et al. (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development, 127:2763-72. (PubMed:10821773)
  91. Reddy S et al. (2001) Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev, 107:69-82. (PubMed:11520664)
  92. Riccomagno MM et al. (2002) Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes Dev, 16:2365-78. (PubMed:12231626)
  93. Rice R et al. (2004) Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. J Clin Invest, 113:1692-700. (PubMed:15199404)
  94. Rowbotham NJ et al. (2009) Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism. Blood, 113:5144-56. (PubMed:19273836)
  95. Rowbotham NJ et al. (2007) Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation. Blood, 109:3757-66. (PubMed:17227833)
  96. Rusiniak ME et al. (1996) Molecular markers near the mouse brachymorphic (bm) gene, which affects connective tissues and bleeding time. Mamm Genome, 7:98-102. (PubMed:8835524)
  97. Sanz-Ezquerro JJ et al. (2000) Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development. Development, 127:4811-23. (PubMed:11044396)
  98. Sarkar L et al. (2000) Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proc Natl Acad Sci U S A, 97:4520-4. (PubMed:10781055)
  99. Shah DK et al. (2004) Reduced thymocyte development in sonic hedgehog knockout embryos. J Immunol, 172:2296-306. (PubMed:14764698)
  100. St-Jacques B et al. (1998) Sonic hedgehog signaling is essential for hair development. Curr Biol, 8:1058-68. (PubMed:9768360)
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  102. Tekki-Kessaris N et al. (2001) Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development, 128:2545-54. (PubMed:11493571)
  103. Tenzen T et al. (2006) The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Dev Cell, 10:647-56. (PubMed:16647304)
  104. Tian H et al. (2004) Dose dependency of Disp1 and genetic interaction between Disp1 and other hedgehog signaling components in the mouse. Development, 131:4021-33. (PubMed:15269168)
  105. Tsukui T et al. (1999) 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, 96:11376-81. (PubMed:10500184)
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  114. Wang Y et al. (2005) Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development, 132:5103-13. (PubMed:16236765)
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  122. Yu J et al. (2002) Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development, 129:5301-12. (PubMed:12399320)
  123. Zhang XM et al. (2001) Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell, 106:781-92. (PubMed:11517919)
  124. Zhang Y et al. (1999) Msx1 is required for the induction of Patched by Sonic hedgehog in the mammalian tooth germ. Dev Dyn, 215:45-53. (PubMed:10340755)
  125. Zhao M et al. (2006) The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling. Mol Cell Biol, 26:6197-208. (PubMed:16880529)

Go Annotations in Tabular Form (Text View) (GO Graph)

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Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IAS Inferred from ancestral sequence
  IBA Inferred from biological aspect of ancestor
  IBD Inferred from biological aspect of descendant
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IKR Inferred from key residues
  IMP Inferred from mutant phenotype
  IMR Inferred from missing residues
  IPI Inferred from physical interaction
  IRD Inferred from rapid divergence
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement


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