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: chicken
Products:     SHH

Top Publications

  1. Riddle R, Johnson R, Laufer E, Tabin C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell. 1993;75:1401-16 pubmed
    ..Like the ZPA, Sonic hedgehog expression leads to the activation of Hox genes. Sonic hedgehog thus appears to function as the signal for antero-posterior patterning in the limb. ..
  2. Bangs F, Welten M, Davey M, Fisher M, Yin Y, Downie H, et al. Identification of genes downstream of the Shh signalling in the developing chick wing and syn-expressed with Hoxd13 using microarray and 3D computational analysis. Mech Dev. 2010;127:428-41 pubmed publisher
    Sonic hedgehog (Shh) signalling by the polarizing region at the posterior margin of the chick wing bud is pivotal in patterning the digits but apart from a few key downstream genes, such as Hoxd13, which is expressed in the posterior ..
  3. Cordero D, Marcucio R, Hu D, Gaffield W, Tapadia M, Helms J. Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes. J Clin Invest. 2004;114:485-94 pubmed
    ..Family members carrying identical mutations in sonic hedgehog (SHH) can exhibit a variety of facial features ranging from cyclopia to subtle midline asymmetries...
  4. Scherz P, Harfe B, McMahon A, Tabin C. The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA cells. Science. 2004;305:396-9 pubmed
    Vertebrate limb outgrowth is driven by a positive feedback loop involving Sonic Hedgehog (Shh), Gremlin, and Fgf4...
  5. Sanz Ezquerro J, Tickle C. Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development. Development. 2000;127:4811-23 pubmed
    The polarising region expresses the signalling molecule sonic hedgehog (Shh), and is an embryonic signalling centre essential for outgrowth and patterning of the vertebrate limb...
  6. Young N, Chong H, Hu D, Hallgrimsson B, Marcucio R. Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape. Development. 2010;137:3405-9 pubmed publisher
    ..Sonic hedgehog (SHH) signaling activity in the vertebrate forebrain and face is thought to contribute to continuous variation in the ..
  7. Moran C, Myers C, Lewis C, Krieg P. Hedgehog regulates angiogenesis of intersegmental vessels through the VEGF signaling pathway. Dev Dyn. 2012;241:1034-42 pubmed publisher
    ..These results demonstrate that Hh is an essential modulator of VEGF expression during developmental angiogenesis...
  8. Bastida M, Sheth R, Ros M. A BMP-Shh negative-feedback loop restricts Shh expression during limb development. Development. 2009;136:3779-89 pubmed publisher
    ..the zone of polarizing activity (ZPA) that controls growth and patterning through the production of sonic hedgehog (SHH)...
  9. Vokes S, Yatskievych T, Heimark R, McMahon J, McMahon A, Antin P, et al. Hedgehog signaling is essential for endothelial tube formation during vasculogenesis. Development. 2004;131:4371-80 pubmed
    ..These results demonstrate a previously uncharacterized role for Hedgehog signaling in vascular development, and identify Hedgehog signaling as an important component of the molecular pathway leading to vascular tube formation. ..

More Information


  1. Spence J, Aycinena J, Del Rio Tsonis K. Fibroblast growth factor-hedgehog interdependence during retina regeneration. Dev Dyn. 2007;236:1161-74 pubmed
    ..responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration...
  2. Vieira C, Garda A, Shimamura K, Martinez S. Thalamic development induced by Shh in the chick embryo. Dev Biol. 2005;284:351-63 pubmed
    ..ZLI has recently been considered to be a possible secondary organizer, effecting its inductions via sonic hedgehog (Shh), a signaling molecule which drives morphogenetic information for the thalamus...
  3. Katsu K, Tokumori D, Tatsumi N, Suzuki A, Yokouchi Y. BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo. Dev Biol. 2012;363:15-26 pubmed publisher
    ..Chicken Dan is expressed in the left side of the node shortly after left-handed Shh expression and before the appearance of asymmetrically expressed genes in the lateral plate mesoderm (LPM)...
  4. Fujiwara N, Duess J, Puri P, Thompson J. Disturbance of SHH signalling pathway during early embryogenesis in the cadmium-induced omphalocele chick model. Pediatr Surg Int. 2013;29:165-70 pubmed publisher
    ..Sonic hedgehog (SHH) signalling plays an important role in vertebrate development, including somitogenesis and thus ventral body wall ..
  5. Lobjois V, Benazeraf B, Bertrand N, Medevielle F, Pituello F. Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development. Dev Biol. 2004;273:195-209 pubmed
    ..Those escaping the caudal neural stem zone, which is expressed to Shh signal, initiate ventral patterning in the neural groove before starting neuronal differentiation in the neural ..
  6. Abzhanov A, Tabin C. Shh and Fgf8 act synergistically to drive cartilage outgrowth during cranial development. Dev Biol. 2004;273:134-48 pubmed
    ..Fgf8 and Shh, signaling molecules known to be important for craniofacial development, are expressed in distinct domains in the ..
  7. Liu F, Placzek M. Axon guidance effects of classical morphogens Shh and BMP7 in the hypothalamo-pituitary system. Neurosci Lett. 2014;562:108-13 pubmed
    ..Here we show that Shh and BMP7, which are expressed in the anterior and posterior hypothalamic ventral midline respectively, together ..
  8. Johnson E, Neely D, Dunn I, Davey M. Direct functional consequences of ZRS enhancer mutation combine with secondary long range SHH signalling effects to cause preaxial polydactyly. Dev Biol. 2014;392:209-20 pubmed publisher
    Sonic hedgehog (SHH) plays a central role in patterning numerous embryonic tissues including, classically, the developing limb bud where it controls digit number and identity...
  9. Luo J, Ju M, Lin J, Yan X, Markus A, Mix E, et al. Cadherin-20 expression by motor neurons is regulated by Sonic hedgehog during spinal cord development. Neuroreport. 2009;20:365-70 pubmed publisher
    ..To investigate the regulation of cadherin-20 expression, Sonic hedgehog (Shh) signaling was altered in chicken spinal cord and hindbrain by in-vivo electroporation...
  10. Kobayashi T, Yasuda K, Araki M. Coordinated regulation of dorsal bone morphogenetic protein 4 and ventral Sonic hedgehog signaling specifies the dorso-ventral polarity in the optic vesicle and governs ocular morphogenesis through fibroblast growth factor 8 upregulation. Dev Growth Differ. 2010;52:351-63 pubmed publisher
    ..and anterior ventral cephalon, and clearly demonstrate that bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) constitute a dorsal-ventral signaling system together with fibroblast growth factor 8 (FGF8)...
  11. McKinnell I, Turmaine M, Patel K. Sonic Hedgehog functions by localizing the region of proliferation in early developing feather buds. Dev Biol. 2004;272:76-88 pubmed
    ..The ectoderm subsequently signals back to the dermis to promote cell division. Sonic Hedgehog (Shh) is a secreted protein expressed in the ectoderm that has previously been implicated in mitogenic and morphogenetic ..
  12. Agius E, Soukkarieh C, Danesin C, Kan P, Takebayashi H, Soula C, et al. Converse control of oligodendrocyte and astrocyte lineage development by Sonic hedgehog in the chick spinal cord. Dev Biol. 2004;270:308-21 pubmed
    ..ventral neuroepithelium and the specification of this lineage depends on the inductive activity of Sonic hedgehog (Shh) produced by ventral midline cells...
  13. Ohta S, Wang B, Mansour S, Schoenwolf G. SHH ventralizes the otocyst by maintaining basal PKA activity and regulating GLI3 signaling. Dev Biol. 2016;420:100-109 pubmed publisher
    ..Among these, Sonic hedgehog (SHH) plays a critical role in determining ventral polarity...
  14. Brito J, Teillet M, Le Douarin N. Induction of mirror-image supernumerary jaws in chicken mandibular mesenchyme by Sonic Hedgehog-producing cells. Development. 2008;135:2311-9 pubmed publisher
    Previous studies have shown that Sonic Hedgehog (Shh) signaling is crucial for the development of the first branchial arch (BA1) into a lower-jaw in avian and mammalian embryos...
  15. Stasiulewicz M, Gray S, Mastromina I, Silva J, Björklund M, Seymour P, et al. A conserved role for Notch signaling in priming the cellular response to Shh through ciliary localisation of the key Shh transducer Smo. Development. 2015;142:2291-303 pubmed publisher
    Notochord-derived Sonic Hedgehog (Shh) is essential for dorsoventral patterning of the overlying neural tube. Increasing concentration and duration of Shh signal induces progenitors to acquire progressively more ventral fates...
  16. Harris M, Williamson S, Fallon J, Meinhardt H, Prum R. Molecular evidence for an activator-inhibitor mechanism in development of embryonic feather branching. Proc Natl Acad Sci U S A. 2005;102:11734-9 pubmed
    ..Here, we describe the interactions between Sonic hedgehog (Shh) and bone morphogenetic protein 2 (Bmp2) signaling during feather barb ridge morphogenesis...
  17. Abzhanov A, Cordero D, Sen J, Tabin C, Helms J. Cross-regulatory interactions between Fgf8 and Shh in the avian frontonasal prominence. Congenit Anom (Kyoto). 2007;47:136-48 pubmed
    ..of the developing avian embryo contains an organizing center, defined by juxtaposition of the Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains...
  18. Stefanov E, Ferrage J, Parchim N, Lee C, Reginelli A, Taché M, et al. Modification of the zone of polarizing activity signal by trypsin. Dev Growth Differ. 2009;51:123-33 pubmed publisher
    ..axis is controlled by the zone of polarizing activity (ZPA) via the expression of Sonic hedgehog (Shh) and along the proximal-distal axis by the apical ectodermal ridge (AER) through the production of fibroblast ..
  19. Balczerski B, Zakaria S, Tucker A, Borycki A, Koyama E, Pacifici M, et al. Distinct spatiotemporal roles of hedgehog signalling during chick and mouse cranial base and axial skeleton development. Dev Biol. 2012;371:203-14 pubmed publisher
    ..floor plate, it has been assumed that their development, like the axial skeleton, is dependent on Sonic hedgehog (Shh) and modulation of bone morphogenetic protein (Bmp) signalling...
  20. Haworth K, Wilson J, Grevellec A, Cobourne M, Healy C, Helms J, et al. Sonic hedgehog in the pharyngeal endoderm controls arch pattern via regulation of Fgf8 in head ectoderm. Dev Biol. 2007;303:244-58 pubmed
    ..b>Shh is locally expressed in pharyngeal endoderm, adjacent to the Fgf8-expressing ectoderm, and is thus a candidate ..
  21. Bumcrot D, Takada R, McMahon A. Proteolytic processing yields two secreted forms of sonic hedgehog. Mol Cell Biol. 1995;15:2294-303 pubmed
    Sonic hedgehog (Shh) is expressed in tissues with known signalling capacities, such as the notochord, the floor plate of the central nervous system, and the zone of polarizing activity in the limb...
  22. Ohuchi H, Nakagawa T, Yamamoto A, Araga A, Ohata T, Ishimaru Y, et al. The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development. 1997;124:2235-44 pubmed
    ..These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs. ..
  23. El Magd M, Allen S, McGonnell I, Mansour A, Otto A, Patel K. Shh regulates chick Ebf1 gene expression in somite development. Gene. 2015;554:87-95 pubmed publisher
    ..Recently, we have proved that cEbf1 expression in feather is regulated by Shh. It is therefore possible that the somitic expression of cEbf1 is controlled by Shh signals from the notochord...
  24. Nakamura T, Aikawa T, Iwamoto Enomoto M, Iwamoto M, Higuchi Y, Pacifici M, et al. Induction of osteogenic differentiation by hedgehog proteins. Biochem Biophys Res Commun. 1997;237:465-9 pubmed
    ..These findings indicate that hedgehog proteins directly act on osteogenic precursor cells and osteoblasts and stimulate osteogenic differentiation of these cells in co-operation with BMPs. ..
  25. Zuniga A, Haramis A, McMahon A, Zeller R. Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds. Nature. 1999;401:598-602 pubmed
    ..Sonic hedgehog (SHH) signalling by the polarizing region modulates fibroblast growth factor (FGF)4 signalling by the posterior AER, ..
  26. Matsubara H, Saito D, Abe G, Yokoyama H, Suzuki T, Tamura K. Upstream regulation for initiation of restricted Shh expression in the chick limb bud. Dev Dyn. 2017;246:417-430 pubmed publisher
    ..The organizing center for limb morphogenesis, the ZPA (zone of polarizing activity), specifically expresses the Shh gene and is restricted to the posterior region of the developing limb bud...
  27. Chinnaiya K, Tickle C, Towers M. Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock. Nat Commun. 2014;5:4230 pubmed publisher
    ..intrinsic cell cycle clock in polarizing region cells of the chick limb bud times the duration of Sonic hedgehog (Shh) expression, which encodes the morphogen specifying digit pattern across the antero-posterior axis (thumb to little ..
  28. Dierker T, Dreier R, Migone M, Hamer S, Grobe K. Heparan sulfate and transglutaminase activity are required for the formation of covalently cross-linked hedgehog oligomers. J Biol Chem. 2009;284:32562-71 pubmed publisher
    Sonic hedgehog (Shh) signaling plays major roles in embryonic development and has also been associated with the progression of certain cancers...
  29. Stott N, Chuong C. Dual action of sonic hedgehog on chondrocyte hypertrophy: retrovirus mediated ectopic sonic hedgehog expression in limb bud micromass culture induces novel cartilage nodules that are positive for alkaline phosphatase and type X collagen. J Cell Sci. 1997;110 ( Pt 21):2691-701 pubmed
    ..Here, we studied the effect of retroviral overexpression of the chicken sonic hedgehog gene (Shh) on the growth and maturation of limb bud cells in micromass cultures...
  30. Wang S, Yu X, Zhang T, Zhang X, Zhang Z, Chen Y. Chick Pcl2 regulates the left-right asymmetry by repressing Shh expression in Hensen's node. Development. 2004;131:4381-91 pubmed
    Asymmetric expression of sonic hedgehog (Shh) in the left side of Hensen's node, a crucial step for specifying the left-right (LR) axis in the chick embryo, is established by the repression of Shh expression in the right side of the node...
  31. Akazawa C, Tsuzuki H, Nakamura Y, Sasaki Y, Ohsaki K, Nakamura S, et al. The upregulated expression of sonic hedgehog in motor neurons after rat facial nerve axotomy. J Neurosci. 2004;24:7923-30 pubmed
    ..Here we report that facial nerve axotomy upregulates Sonic hedgehog (Shh) and its receptor Smoothened (Smo) in facial motor neurons of adult rats, whereas facial nerve axotomy does not ..
  32. Fliniaux I, Viallet J, Dhouailly D. Signaling dynamics of feather tract formation from the chick somatopleure. Development. 2004;131:3955-66 pubmed
    ..The same result was obtained with the graft of Shh-producing cells, but Noggin and Shh are both required in order to change the future amnion into a feather-bearing ..
  33. Zhulyn O, Li D, Deimling S, Vakili N, Mo R, Puviindran V, et al. A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell. 2014;29:241-9 pubmed publisher
    The patterning and growth of the embryonic vertebrate limb is dependent on Sonic hedgehog (Shh), a morphogen that regulates the activity of Gli transcription factors...
  34. Liu F, Placzek M, Xu H. Axon guidance effect of classical morphogens Shh and BMP7 in the hypothalamo-pituitary system. Neurosci Lett. 2013;553:104-9 pubmed publisher
    ..Here we show that Shh and BMP7, which are from the anterior and posterior hypothalamic ventral midline respectively, together repel ..
  35. Zhang X, Yang X. Temporal and spatial effects of Sonic hedgehog signaling in chick eye morphogenesis. Dev Biol. 2001;233:271-90 pubmed
    ..Previous studies have suggested that midline tissue-derived Sonic hedgehog (Shh) molecules play critical roles in establishing the bilateral eye fields and in determining the proximal--distal ..
  36. Son E, Ma J, Ankamreddy H, Shin J, Choi J, Wu D, et al. Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea. Proc Natl Acad Sci U S A. 2015;112:3746-51 pubmed publisher
    ..Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species...
  37. Craven S, Lim K, Ye W, Engel J, de Sauvage F, Rosenthal A. Gata2 specifies serotonergic neurons downstream of sonic hedgehog. Development. 2004;131:1165-73 pubmed
    ..Here, we identify a Sonic hedgehog (Shh)-regulated cascade of transcription factors that acts to generate a specific subset of 5-HT neurons...
  38. Stamataki D, Ulloa F, Tsoni S, Mynett A, Briscoe J. A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube. Genes Dev. 2005;19:626-41 pubmed
    ..In ventral regions of the spinal cord, Sonic Hedgehog (Shh) is such a signal and controls the emergence, in precise spatial order, of distinct neuronal subtypes...
  39. Afonso N, Catala M. Sonic hedgehog and retinoic acid are not sufficient to induce motoneuron generation in the avian caudal neural tube. Dev Biol. 2005;279:356-67 pubmed
    ..The absence of MNs is not due to a defective notochordal induction since Sonic Hedgehog (SHH) signaling is intact and the caudal notochord is able to induce ectopic MNs when grafted laterally to a host neural ..
  40. Grevellec A, Graham A, Tucker A. Shh signalling restricts the expression of Gcm2 and controls the position of the developing parathyroids. Dev Biol. 2011;353:194-205 pubmed publisher
    ..In this paper we investigate the role of Shh signalling in patterning the vertebrate pharyngeal pouches, and show that Hh signalling may be involved in ..
  41. Wada N, Nohno T. Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4. Dev Dyn. 2001;221:402-11 pubmed
    The interactions of Sonic hedgehog (Shh) and fibroblast growth factor (FGF) play important roles in vertebrate limb pattern formation...
  42. Guan W, Wang G, Scott S, Condic M. Shh influences cell number and the distribution of neuronal subtypes in dorsal root ganglia. Dev Biol. 2008;314:317-28 pubmed publisher
    ..Here we demonstrate that Sonic hedgehog (Shh) contributes to patterning early DRG cells...
  43. Low W, Wang C, Pan Y, Huang X, Chen J, Wang B. The decoupling of Smoothened from Galphai proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning. Dev Biol. 2008;321:188-96 pubmed publisher
    ..appears to significantly reduce Hh pathway activity in Ptc(-/-) mouse embryonic fibroblasts and the NIH3T3-based Shh-light cells, it fails to derepress Shh- or a Smo-agonist-induced inhibition of Gli3 protein processing, a known in ..
  44. Kawakami Y, Ishikawa T, Shimabara M, Tanda N, Enomoto Iwamoto M, Iwamoto M, et al. BMP signaling during bone pattern determination in the developing limb. Development. 1996;122:3557-66 pubmed
  45. Yang C, Li X, Liu Y, Li H, Guo Z, Lin J. Sonic hedgehog overexpression regulates the neuroepithelial cells proliferation in the spinal cord of dorsal regions during chicken embryo development. Neuro Endocrinol Lett. 2015;36:380-6 pubmed
    Sonic hedgehog(SHH) is early expressed in the floor plate and notochord during the development of chicken embryo, which is required for the establishment of dorsal axis and the formation of spinal cord, but the mechanism of SHH affecting ..
  46. Franz Odendaal T. Toward understanding the development of scleral ossicles in the chicken, Gallus gallus. Dev Dyn. 2008;237:3240-51 pubmed publisher
    ..transcriptase polymerase chain reaction of candidate genes identified significant increases in sonic hedgehog (SHH) expression...
  47. Spence J, Madhavan M, Ewing J, Jones D, Lehman B, Del Rio Tsonis K. The hedgehog pathway is a modulator of retina regeneration. Development. 2004;131:4607-21 pubmed
    ..This type of regeneration is also stimulated by Fgf2, but we show that it can be activated by Sonic hedgehog (Shh) overexpression when no ectopic Fgf2 is present...
  48. Bonnin M, Laclef C, Blaise R, Eloy Trinquet S, Relaix F, Maire P, et al. Six1 is not involved in limb tendon development, but is expressed in limb connective tissue under Shh regulation. Mech Dev. 2005;122:573-85 pubmed
    ..Finally, we found that the posterior domain of Six1 in connective tissue is adjacent to that of the secreted factor Sonic hedgehog and that Sonic hedgehog is necessary and sufficient for Six1 expression in posterior limb regions. ..
  49. Cayuso J, Ulloa F, Cox B, Briscoe J, Marti E. The Sonic hedgehog pathway independently controls the patterning, proliferation and survival of neuroepithelial cells by regulating Gli activity. Development. 2006;133:517-28 pubmed
    ..Blockade of Shh signaling or inhibition of Gli activity results in cell autonomous decreases in progenitor proliferation and ..
  50. Resende T, Ferreira M, Teillet M, Tavares A, Andrade R, Palmeirim I. Sonic hedgehog in temporal control of somite formation. Proc Natl Acad Sci U S A. 2010;107:12907-12 pubmed publisher
    ..independently of embryonic midline structures and the signaling molecules produced therein, namely Sonic hedgehog (Shh)...
  51. Benouaiche L, Gitton Y, Vincent C, Couly G, Levi G. Sonic hedgehog signalling from foregut endoderm patterns the avian nasal capsule. Development. 2008;135:2221-5 pubmed publisher
    ..We show that Shh expression in the most rostral zone of the endoderm, endoderm zone I (EZ-I), is necessary to induce the formation ..
  52. Hutson M, Sackey F, Lunney K, Kirby M. Blocking hedgehog signaling after ablation of the dorsal neural tube allows regeneration of the cardiac neural crest and rescue of outflow tract septation. Dev Biol. 2009;335:367-73 pubmed publisher
    ..This disruption of dorsal-ventral neural patterning permits a new wave of migratory cardiac neural crest-like cells. ..
  53. Cairns D, Sato M, Lee P, Lassar A, Zeng L. A gradient of Shh establishes mutually repressing somitic cell fates induced by Nkx3.2 and Pax3. Dev Biol. 2008;323:152-65 pubmed publisher
    Wnt and Sonic Hedgehog (Shh) signals are known to pattern the somite into dermomyotomal, myotomal and sclerotomal cell fates...