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Gene Review

shha  -  sonic hedgehog a

Danio rerio

Synonyms: SHHA, SO:0000704, Sonic hedgehog protein A, VHH-1, fc83d08, ...
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Disease relevance of shha

  • This second wave generates amacrine cells expressing shh, and although it overlaps temporally with the first wave, it does not depend on it, as it occurs in the absence of ganglion cells [1].

High impact information on shha

  • We have isolated a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh) from zebrafish and rat, termed vhh-1. vhh-1 is expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme [2].
  • These zebrafish morphants show Rac hyperactivation and progress faster through epiboly, leading to tailbud-stage embryos that have a narrow axis and an enlarged tailbud with expanded bmp4 and shh expression [3].
  • Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression [4].
  • These results implicate shh and bmp2b signaling in the proliferation and/or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin [4].
  • We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme [4].

Biological context of shha

  • Embryos affected by cadmium-exposure demonstrated a down-regulation in shh expression [5].
  • We report here the characterization of a zebrafish Gli2 expression in slow and fast muscle cells and the study of the roles of Hedgehogs and Gli2 in zebrafish muscle development using two mutant strains; sonic-you (syu) and you-too (yot), respective for sonic hedgehog (shh) and Gli2 mutation [6].
  • Furthermore an enhancer of the shh gene, which controls ventral neural tube expression, is responsive to Cyc signal transducers [7].
  • The relative organization of ache, eng2, and shh genes is conserved between zebrafish and mammals and defines a synteny [8].
  • This pattern of expression suggests that shh may be involved in the control of scale morphogenesis and differentiation in relationship with the formation of the epidermal fold in the posterior region [9].

Anatomical context of shha

  • We report that Hh signaling is necessary between 10 and 15 h of development for induction of the zebrafish adenohypophysis, a time when shh is expressed only in neural tissue [10].
  • In yot mutant embryos, development of slow muscles was completely blocked, whereas in syu mutant embryos, a small number of slow muscle cells could still form, suggesting that other Hhs were also involved in slow muscle induction [6].
  • Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord [2].
  • Here, we describe formation of the ZLI in zebrafish in relation to expression of sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh), and to development of the forebrain regions that flank the ZLI: the prethalamus and thalamus [11].
  • The expression domain of ptc1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc1 [12].

Associations of shha with chemical compounds


Regulatory relationships of shha


Other interactions of shha

  • The number of GFP-expressing cells measured by flow cytometry decreased, and expression of neurogenin-1, a downstream target of the shh signaling pathway, was down-regulated, providing additional supporting data on the effects of cadmium on shh [5].
  • We have shown that RA exposure during the early stages of pectoral fin development first results in a rapid decrease or complete loss of shh/ptc1 expression [14].
  • This suggests that oep is required downstream or in parallel to shh signaling [15].
  • Together, these results suggest a requirement of shh/vhh-1 protein for the spatial regulation of nk2.2 expression [16].
  • In addition, we show that shh and twhh display both unique and redundant functions during diencephalic patterning [11].

Analytical, diagnostic and therapeutic context of shha

  • Ectopic activation of the shh promoter occurs in response to expression of Cyc signal transducers in the chick neural tube [7].
  • To investigate the regulatory mechanisms underlying the pattern of shh expression, we carried out a systematic analysis of the intronic regulatory sequences of zebrafish shh using stable transgenesis [17].
  • Transplantation experiments illustrated that the effects of irx1a on shh expression are both cell-autonomous and non-cell-autonomous [18].


  1. Sonic hedgehog, secreted by amacrine cells, acts as a short-range signal to direct differentiation and lamination in the zebrafish retina. Shkumatava, A., Fischer, S., Müller, F., Strahle, U., Neumann, C.J. Development (2004) [Pubmed]
  2. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Roelink, H., Augsburger, A., Heemskerk, J., Korzh, V., Norlin, S., Ruiz i Altaba, A., Tanabe, Y., Placzek, M., Edlund, T., Jessell, T.M. Cell (1994) [Pubmed]
  3. The zebrafish homologue of mammalian chimerin Rac-GAPs is implicated in epiboly progression during development. Leskow, F.C., Holloway, B.A., Wang, H., Mullins, M.C., Kazanietz, M.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine. Quint, E., Smith, A., Avaron, F., Laforest, L., Miles, J., Gaffield, W., Akimenko, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) embryos. Yu, R.M., Lin, C.C., Chan, P.K., Chow, E.S., Murphy, M.B., Chan, B.P., Müller, F., Strähle, U., Cheng, S.H. Toxicol. Sci. (2006) [Pubmed]
  6. Gli2 mediation of hedgehog signals in slow muscle induction in zebrafish. Du, S.J., Dienhart, M. Differentiation (2001) [Pubmed]
  7. Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS. Müller, F., Albert, S., Blader, P., Fischer, N., Hallonet, M., Strähle, U. Development (2000) [Pubmed]
  8. Zebrafish acetylcholinesterase is encoded by a single gene localized on linkage group 7. Gene structure and polymorphism; molecular forms and expression pattern during development. Bertrand, C., Chatonnet, A., Takke, C., Yan, Y.L., Postlethwait, J., Toutant, J.P., Cousin, X. J. Biol. Chem. (2001) [Pubmed]
  9. Scale development in fish: a review, with description of sonic hedgehog (shh) expression in the zebrafish (Danio rerio). Sire, J.Y., Akimenko, M.A. Int. J. Dev. Biol. (2004) [Pubmed]
  10. Multiple roles for Hedgehog signaling in zebrafish pituitary development. Sbrogna, J.L., Barresi, M.J., Karlstrom, R.O. Dev. Biol. (2003) [Pubmed]
  11. Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon. Scholpp, S., Wolf, O., Brand, M., Lumsden, A. Development (2006) [Pubmed]
  12. Involvement of the sonic hedgehog, patched 1 and bmp2 genes in patterning of the zebrafish dermal fin rays. Laforest, L., Brown, C.W., Poleo, G., Géraudie, J., Tada, M., Ekker, M., Akimenko, M.A. Development (1998) [Pubmed]
  13. A temperature-sensitive mutation in the nodal-related gene cyclops reveals that the floor plate is induced during gastrulation in zebrafish. Tian, J., Yam, C., Balasundaram, G., Wang, H., Gore, A., Sampath, K. Development (2003) [Pubmed]
  14. Exogenous retinoic acid induces a stage-specific, transient and progressive extension of Sonic hedgehog expression across the pectoral fin bud of zebrafish. Hoffman, L., Miles, J., Avaron, F., Laforest, L., Akimenko, M.A. Int. J. Dev. Biol. (2002) [Pubmed]
  15. The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Schier, A.F., Neuhauss, S.C., Helde, K.A., Talbot, W.S., Driever, W. Development (1997) [Pubmed]
  16. Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. Barth, K.A., Wilson, S.W. Development (1995) [Pubmed]
  17. Cooperation of sonic hedgehog enhancers in midline expression. Ertzer, R., Müller, F., Hadzhiev, Y., Rathnam, S., Fischer, N., Rastegar, S., Strähle, U. Dev. Biol. (2007) [Pubmed]
  18. The homeobox gene irx1a is required for the propagation of the neurogenic waves in the zebrafish retina. Cheng, C.W., Yan, C.H., Hui, C.C., Strähle, U., Cheng, S.H. Mech. Dev. (2006) [Pubmed]
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