Shh

Summary

Gene Symbol: Shh
Description: sonic hedgehog
Alias: HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC, TPT, TPTPS, sonic hedgehog protein, shh unprocessed N-terminal signaling and C-terminal autoprocessing domains, sonic hedgehog homolog
Species: human
Products:     Shh

Top Publications

  1. Kusano K, Pola R, Murayama T, Curry C, Kawamoto A, Iwakura A, et al. Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling. Nat Med. 2005;11:1197-204 pubmed
    Sonic hedgehog (Shh) is a crucial regulator of organ development during embryogenesis...
  2. Yoo Y, Kang M, Kim J, Oh S. Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-beta-mediated activation of the ALK5-Smad 3 pathway. Carcinogenesis. 2008;29:480-90 pubmed publisher
    ..In this study, we investigated the impact of transforming growth factor (TGF)-beta signaling on the sonic hedgehog (Shh)-mediated invasion of gastric cancer cells...
  3. Yoshikawa K, Shimada M, Miyamoto H, Higashijima J, Miyatani T, Nishioka M, et al. Sonic hedgehog relates to colorectal carcinogenesis. J Gastroenterol. 2009;44:1113-7 pubmed publisher
    ..In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer...
  4. Maity T, Fuse N, Beachy P. Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. Proc Natl Acad Sci U S A. 2005;102:17026-31 pubmed
    ..The N-terminal domain (ShhNp) of Sonic hedgehog protein, generated by cholesterol-dependent autoprocessing and modification at the C terminus and by palmitate ..
  5. Martinez M, Larbret F, Zobairi F, Coulombe J, Debili N, Vainchenker W, et al. Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood. 2006;108:3012-20 pubmed
  6. Lamm M, Catbagan W, Laciak R, Barnett D, Hebner C, Gaffield W, et al. Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Dev Biol. 2002;249:349-66 pubmed
    ..We show here that ductal bud formation is associated with focused expression of Sonic hedgehog (Shh) in the epithelium of nascent prostate buds and in the growing tips of elongating prostate ducts...
  7. Gutiérrez Frías C, Sacedon R, Hernández López C, Cejalvo T, Crompton T, Zapata A, et al. Sonic hedgehog regulates early human thymocyte differentiation by counteracting the IL-7-induced development of CD34+ precursor cells. J Immunol. 2004;173:5046-53 pubmed
    ..In this study, we investigate the potential role of Sonic hedgehog (Shh) in human intrathymic T cell maturation...
  8. Lettice L, Horikoshi T, Heaney S, van Baren M, van der Linde H, Breedveld G, et al. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natl Acad Sci U S A. 2002;99:7548-53 pubmed
    ..A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits...
  9. 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. ..

More Information

Publications64

  1. Alvarez J, Dodelet Devillers A, Kebir H, Ifergan I, Fabre P, Terouz S, et al. The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science. 2011;334:1727-31 pubmed publisher
    ..Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis. ..
  2. Traiffort E, Dubourg C, Faure H, Rognan D, Odent S, Durou M, et al. Functional characterization of sonic hedgehog mutations associated with holoprosencephaly. J Biol Chem. 2004;279:42889-97 pubmed
    Mutations of the developmental gene Sonic hedgehog (SHH) and alterations of SHH signaling have been associated with holoprosencephaly (HPE), a rare disorder characterized by a large spectrum of brain and craniofacial anomalies...
  3. Thayer S, di Magliano M, Heiser P, Nielsen C, Roberts D, Lauwers G, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425:851-6 pubmed
    ..Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of ..
  4. Lettice L, Heaney S, Purdie L, Li L, de Beer P, Oostra B, et al. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet. 2003;12:1725-35 pubmed
    ..preaxial polydactyly, a frequently observed congenital limb malformation, results from point mutations in a Shh regulatory element...
  5. Watkins D, Berman D, Burkholder S, Wang B, Beachy P, Baylin S. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003;422:313-7 pubmed
    ..Prompted by the requirement for sonic hedgehog (Shh) signalling in lung development, we investigated a role for this pathway in regeneration and carcinogenesis of ..
  6. Lettice L, Hill A, Devenney P, Hill R. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet. 2008;17:978-85 pubmed
    ..of this novel class of mutations and is caused by ectopic expression of the signalling molecule Sonic Hedgehog (SHH) in the developing limb bud...
  7. Huang C, Hsiao H, Chu Y, Ye Y, Chen X. Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum. J Biol Chem. 2013;288:25330-9 pubmed publisher
    ..have nonredundant functions in ERAD with derlin2 being an essential functional partner for HRD1-mediated ERAD of SHH and NHK...
  8. Onishi H, Kai M, Odate S, Iwasaki H, Morifuji Y, Ogino T, et al. Hypoxia activates the hedgehog signaling pathway in a ligand-independent manner by upregulation of Smo transcription in pancreatic cancer. Cancer Sci. 2011;102:1144-50 pubmed publisher
    ..Hypoxia upregulated the transcription of Sonic hedgehog (Shh), Smoothened (Smo), Gli1 and matrix metalloproteinase9 (MMP9) and increased the invasiveness of PDAC...
  9. Oro A, Higgins K, Hu Z, Bonifas J, Epstein E, Scott M. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science. 1997;276:817-21 pubmed
    ..Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimic loss of ptc function...
  10. Eichenmüller M, Gruner I, Hagl B, Häberle B, Müller Höcker J, Von Schweinitz D, et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology. 2009;49:482-90 pubmed publisher
  11. Bar E, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells. 2007;25:2524-33 pubmed
    ..b>Shh ligand was expressed in some primary tumors, and in GBM-derived neurospheres, suggesting a potential mechanism for ..
  12. Sims Mourtada J, Izzo J, Ajani J, Chao K. Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene. 2007;26:5674-9 pubmed
    ..These results suggest that the Hh pathway may be a target to overcome MDR and increase chemotherapeutic response...
  13. Kumamoto H, Ohki K, Ooya K. Expression of Sonic hedgehog (SHH) signaling molecules in ameloblastomas. J Oral Pathol Med. 2004;33:185-90 pubmed
    To clarify the roles of Sonic hedgehog (SHH) signal transduction in oncogenesis and cytodifferentiation of odontogenic tumors, expression of SHH, Patched (PTC), Smoothened (SMO), and GLI1 was analyzed in ameloblastomas as well as in ..
  14. Qualtrough D, Buda A, Gaffield W, Williams A, Paraskeva C. Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment. Int J Cancer. 2004;110:831-7 pubmed
    ..These data suggest that autocrine Hh signalling can increase aberrant cell survival in colorectal tumour cells and may be a novel target for colon cancer therapy using drugs such as cyclopamine. ..
  15. Ma X, Chen K, Huang S, Zhang X, Adegboyega P, Evers B, et al. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis. 2005;26:1698-705 pubmed
    ..The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer ..
  16. Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer S, et al. Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nat Genet. 1996;14:357-60 pubmed
    ..b>HPE3 on chromosome 7q36 is one of at least four different loci implicated in HPE...
  17. Shahi M, Afzal M, Sinha S, Eberhart C, Rey J, Fan X, et al. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. BMC Cancer. 2010;10:614 pubmed publisher
    The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer...
  18. Shaw A, Gipp J, Bushman W. The Sonic Hedgehog pathway stimulates prostate tumor growth by paracrine signaling and recapitulates embryonic gene expression in tumor myofibroblasts. Oncogene. 2009;28:4480-90 pubmed publisher
    ..The presence of robust Sonic Hedgehog (Shh) expression in both normal prostate and localized cancer challenged us to explain the unique growth-promoting ..
  19. Yoo Y, Kang M, Lee H, Kim B, Park J, Kim H, et al. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 2011;71:7061-70 pubmed publisher
    Activation of sonic hedgehog (Shh) signaling has been implicated in progression of a variety of tumors. In this study, we elucidated a role for Shh in the invasion of gastric tumors and determined the mechanism by which Shh is regulated...
  20. 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...
  21. 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...
  22. Sagai T, Masuya H, Tamura M, Shimizu K, Yada Y, Wakana S, et al. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog ( Shh). Mamm Genome. 2004;15:23-34 pubmed
    Polarized expression of the Sonic hedgehog ( Shh) gene in the posterior mesenchyme is essential for pattern formation in the appendages of higher vertebrates, from teleost fins to tetrapod limb buds...
  23. Teng H, Chopp M, Hozeska Solgot A, Shen L, Lu M, Tang C, et al. Tissue plasminogen activator and plasminogen activator inhibitor 1 contribute to sonic hedgehog-induced in vitro cerebral angiogenesis. PLoS ONE. 2012;7:e33444 pubmed publisher
    ..endothelial cells (MBECs) and a capillary-like tube formation assay, we investigated whether the sonic hedgehog (Shh) signaling pathway is coupled with the plasminogen/plasmin system in mediating cerebral angiogenesis...
  24. Pepinsky R, Zeng C, Wen D, Rayhorn P, Baker D, Williams K, et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem. 1998;273:14037-45 pubmed
    ..The observation that an extracellular protein such as Shh is palmitoylated is highly unusual and further adds to the complex nature of this protein.
  25. Dimmler A, Brabletz T, Hlubek F, Häfner M, Rau T, Kirchner T, et al. Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and gastric mucosa maintenance, is up-regulated in acidic conditions. Lab Invest. 2003;83:1829-37 pubmed
    ..Sonic hedgehog (Shh) has recently been implicated as a crucial factor in gastric organogenesis and gland differentiation...
  26. Berman D, Karhadkar S, Maitra A, Montes De Oca R, Gerstenblith M, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846-51 pubmed
    ..Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression. ..
  27. Kanda S, Mochizuki Y, Suematsu T, Miyata Y, Nomata K, Kanetake H. Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase. J Biol Chem. 2003;278:8244-9 pubmed
    Sonic hedgehog (Shh) acts as a morphogen in many cell types. Recent studies have shown that hedgehog signaling is involved in vascular development as well as postnatal angiogenesis...
  28. Bhardwaj G, Murdoch B, Wu D, Baker D, Williams K, Chadwick K, et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001;2:172-80 pubmed
    ..Conversely, Sonic hedgehog (Shh) treatment induced the expansion of pluripotent human hematopoietic repopulating cells detected in immunodeficient ..
  29. Chuang P, McMahon A. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature. 1999;397:617-21 pubmed
    ..Our findings support a model in which Hip attenuates Hedgehog signalling as a result of binding to Hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any Hedgehog signal. ..
  30. Hwang S, Thangapandian S, Lee K. Molecular dynamics simulations of sonic hedgehog-receptor and inhibitor complexes and their applications for potential anticancer agent discovery. PLoS ONE. 2013;8:e68271 pubmed publisher
    The sonic hedgehog (Shh) signaling pathway is necessary for a variety of development and differentiation during embryogenesis as well as maintenance and renascence of diverse adult tissues...
  31. Mao L, Xia Y, Zhou Y, Dai R, Yang X, Duan S, et al. A critical role of Sonic Hedgehog signaling in maintaining the tumorigenicity of neuroblastoma cells. Cancer Sci. 2009;100:1848-55 pubmed publisher
    Accumulated evidence suggests a major role for the activation of the Sonic Hedgehog (SHH) signaling pathway in the development of neural crest stem cells that give rise to the sympathetic nervous system...
  32. Chen W, Tang T, Eastham Anderson J, Dunlap D, Alicke B, Nannini M, et al. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells. Proc Natl Acad Sci U S A. 2011;108:9589-94 pubmed publisher
  33. Fendrich V, Waldmann J, Esni F, Ramaswamy A, Mullendore M, Buchholz M, et al. Snail and Sonic Hedgehog activation in neuroendocrine tumors of the ileum. Endocr Relat Cancer. 2007;14:865-74 pubmed
    ..In this study, we examined whether Snail and Sonic Hedgehog (SHH) are expressed in neuroendocrine tumors (NETs) of the ileum...
  34. Bailey J, Mohr A, Hollingsworth M. Sonic hedgehog paracrine signaling regulates metastasis and lymphangiogenesis in pancreatic cancer. Oncogene. 2009;28:3513-25 pubmed publisher
    Sonic hedgehog (SHH) expression is tightly regulated throughout development...
  35. Bosanac I, Maun H, Scales S, Wen X, Lingel A, Bazan J, et al. The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling. Nat Struct Mol Biol. 2009;16:691-7 pubmed publisher
    ..The crystal structures of human HHIP alone and bound to Sonic hedgehog (SHH) now reveal that HHIP is comprised of two EGF domains and a six-bladed beta-propeller domain...
  36. Stewart G, Lowrey J, Wakelin S, Fitch P, Lindey S, Dallman M, et al. Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells. J Immunol. 2002;169:5451-7 pubmed
    Sonic hedgehog (Shh) is important in the growth and differentiation of a variety of cell types, including the development of T cells in the thymus...
  37. Ma X, Sheng T, Zhang Y, Zhang X, He J, Huang S, et al. Hedgehog signaling is activated in subsets of esophageal cancers. Int J Cancer. 2006;118:139-48 pubmed
    ..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 ..
  38. Yamazaki M, Nakamura K, Mizukami Y, Ii M, Sasajima J, Sugiyama Y, et al. Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells. Cancer Sci. 2008;99:1131-8 pubmed publisher
    ..Several recent observations suggest the involvement of sonic hedgehog (SHH) in postnatal neovascularization...
  39. Roessler E, El Jaick K, Dubourg C, Vélez J, Solomon B, Pineda Alvarez D, et al. The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. Hum Mutat. 2009;30:E921-35 pubmed publisher
    Mutations within either the SHH gene or its related pathway components are the most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with the essential functions of this ..
  40. Stecca B, Mas C, Clement V, Zbinden M, Correa R, Piguet V, et al. Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci U S A. 2007;104:5895-900 pubmed
    ..Here we report that SONIC HEDGEHOG (SHH)-GLI signaling is active in the matrix of human hair follicles, and that it is required for the normal ..
  41. Chen X, Tukachinsky H, Huang C, Jao C, Chu Y, Tang H, et al. Processing and turnover of the Hedgehog protein in the endoplasmic reticulum. J Cell Biol. 2011;192:825-38 pubmed publisher
    ..Thus, processing of the Hh precursor competes with its rapid degradation, explaining the impaired Hh signaling of processing-defective mutants, such as those causing human holoprosencephaly. ..
  42. Hardy R, Resh M. Identification of N-terminal residues of Sonic Hedgehog important for palmitoylation by Hedgehog acyltransferase. J Biol Chem. 2012;287:42881-9 pubmed publisher
    Sonic Hedgehog (Shh) is a secreted morphogen that regulates embryonic development...
  43. Sanchez P, Hernandez A, Stecca B, Kahler A, DeGueme A, Barrett A, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci U S A. 2004;101:12561-6 pubmed
    ..Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)-GLI signaling pathway is implicated in prostate cancer...
  44. He H, Chen J, Chen X, Qin G, Cai C, Liang Y, et al. Expression of hedgehog pathway components is associated with bladder cancer progression and clinical outcome. Pathol Oncol Res. 2012;18:349-55 pubmed publisher
    ..The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 ..
  45. Lauth M, Bergström A, Shimokawa T, Tostar U, Jin Q, Fendrich V, et al. DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS. Nat Struct Mol Biol. 2010;17:718-25 pubmed publisher
    ..the molecular cross-talk between RAS and HH signaling and found that, although mutant RAS induces or enhances SHH expression and favors paracrine HH signaling, it antagonizes autocrine HH signal transduction...
  46. Buglino J, Resh M. Hhat is a palmitoylacyltransferase with specificity for N-palmitoylation of Sonic Hedgehog. J Biol Chem. 2008;283:22076-88 pubmed publisher
    Palmitoylation of Sonic Hedgehog (Shh) is critical for effective long- and short-range signaling...
  47. Zunich S, Douglas T, Valdovinos M, Chang T, Bushman W, Walterhouse D, et al. Paracrine sonic hedgehog signalling by prostate cancer cells induces osteoblast differentiation. Mol Cancer. 2009;8:12 pubmed publisher
    Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis...
  48. Syn W, Jung Y, Omenetti A, Abdelmalek M, Guy C, Yang L, et al. Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease. Gastroenterology. 2009;137:1478-1488.e8 pubmed publisher
    ..Immature ductular cells were exposed to Sonic hedgehog (Shh) in the presence or absence of the Hh inhibitor cyclopamine to determine whether Hh-pathway activation directly ..
  49. 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...
  50. Bolaños A, Milla C, Lira J, Ramirez R, Checa M, Barrera L, et al. Role of Sonic Hedgehog in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2012;303:L978-90 pubmed publisher
    ..Here we evaluated the expression of Sonic Hedgehog (SHH), Patched-1, Smoothened, and transcription factors glioma-associated oncogene homolog (GLI)1 and GLI2 by RT-PCR, as ..
  51. 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...
  52. Shimo T, Matsumoto K, Takabatake K, Aoyama E, Takebe Y, Ibaragi S, et al. The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. PLoS ONE. 2016;11:e0151731 pubmed publisher
    Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis...
  53. Chang J, Xu W, Liu G, Du X, Li X. Downregulation of Rab23 in Prostate Cancer Inhibits Tumor Growth In Vitro and In Vivo. Oncol Res. 2017;25:241-248 pubmed publisher
    ..In addition, downregulation of Rab23 significantly downregulated the protein expression levels of Shh and Gli1...
  54. Laufer E, Kesper D, Vortkamp A, King P. Sonic hedgehog signaling during adrenal development. Mol Cell Endocrinol. 2012;351:19-27 pubmed publisher
    It has been speculated for a number of years that Sonic hedgehog (Shh) signaling plays an important role in adrenal development...
  55. Chu Q, Yan Z, Zhang J, Usman T, Zhang Y, Liu H, et al. Association of SNP rs80659072 in the ZRS with polydactyly in Beijing You chickens. PLoS ONE. 2017;12:e0185953 pubmed publisher
    ..The G/T mutation of SNP rs80659072 in the Shh long-range regulator of GGA2 is highly associated with the polydactyly phenotype in some chicken breeds...