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SHH  -  sonic hedgehog

Gallus gallus

 
 
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Disease relevance of SHH

  • Moreover, elevated HES1 expression promotes progenitor cell proliferation and prevents overproduction of retinal ganglion cells owing to the loss of VEGF or sonic hedgehog (SHH), another signal that suppresses ganglion cell development [1].
  • This demonstration of EMT in avian lip development lays important groundwork for understanding the causes of human cleft lip and analyzing the mechanism of action of growth factors, such as SHH and BMPs, that have been shown (J. A. Helms et al., 1997, Dev. Biol. 187, 25-35) to be involved in avian lip confluence [2].
 

High impact information on SHH

  • Our results suggest that the induction of floor plate cells and motor neurons by the notochord in vivo is mediated by exposure of neural plate cells to different concentrations of the amino-terminal product of SHH autoproteolytic cleavage [3].
  • We have found that both floor plate cells and motor neurons are induced by the amino-terminal cleavage product of SHH (SHH-N) [3].
  • Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm [4].
  • SHH and BMP4 proteins negatively regulate each other's transcription, resulting in a strict complementarity between these two gene patterns on each side of the node [5].
  • After a gap of several hours, SHH induces polarized gene activities in the left paraxial mesoderm [5].
 

Biological context of SHH

  • We undertook a series of experiments to test the hypothesis that modifying the activity of the SHH signaling pathway at discrete periods of embryonic development could account for the phenotypic spectrum of HPE [6].
  • Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH [7].
  • Based on previous and current findings, we propose that HES1 serves as a convergent signaling node within early retinal progenitor cells to integrate various cell-extrinsic cues, including VEGF and SHH, in order to control cell proliferation and neuronal specification [1].
  • We find that SHH and FGF8 have strong synergistic effects on chondrogenesis in vitro and are sufficient to promote outgrowth and chondrogenesis in vivo, suggesting a very specific role for these molecules in producing the elongated beak structures during chick facial development [8].
  • SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system [9].
 

Anatomical context of SHH

  • Thus, some aspects of mesoderm A-P patterning can occur in the absence of SHH and factors normally expressed in the apical ridge [10].
  • In contrast, SHH is not required for the induction of Hoxd11 or Hoxd13 expression, since expression of both these genes was detected in the mutant limb buds [10].
  • 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 tube [11].
  • Addition of SHH to primary cultures of myoblasts resulted in an increase in the proportion of myoblasts that incorporate bromodeoxyuridine, resulting in an increase of myotube number [12].
  • Removing the source of Sonic Hedgehog (SHH) by ablating the floor plate and/or notochord, or inhibiting SHH function using an antibody that blocks SHH bioactivity results in loss of ventral inner ear structures [13].
 

Associations of SHH with chemical compounds

  • Retinoic acid and Sonic Hedgehog (SHH) can act as polarizing signals; when applied anteriorly in the limb bud, they induce mirror-image digit duplications and ectopic Bmp-2 expression in anterior mesenchyme [14].
  • Providing ectopic SHH protein, RA or ZPA grafts overcome the effects of blocking PKC with chelerythrine and resulted in a rescue of the wing morphology [15].
 

Other interactions of SHH

  • Bmp2 expression was also not detected in mutant limb mesoderm, consistent with the hypothesis that SHH induces its expression [10].
  • Cloning and expression pattern of chicken Pitx2: a new component in the SHH signaling pathway controlling embryonic heart looping [16].
  • We found that retrovirally overexpressed SHH in the limb bud induced the extension of the expression domain of the Pax-3 gene, then that of the MyoD gene and finally that of the myosin protein [12].
  • SHH is also able to maintain cTwist expression but only in the presence of the AER [17].
 

Analytical, diagnostic and therapeutic context of SHH

  • In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments [9].

References

  1. VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation. Hashimoto, T., Zhang, X.M., Chen, B.Y., Yang, X.J. Development (2006) [Pubmed]
  2. Epithelial-mesenchymal transformation is the mechanism for fusion of the craniofacial primordia involved in morphogenesis of the chicken lip. Sun, D., Baur, S., Hay, E.D. Dev. Biol. (2000) [Pubmed]
  3. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Roelink, H., Porter, J.A., Chiang, C., Tanabe, Y., Chang, D.T., Beachy, P.A., Jessell, T.M. Cell (1995) [Pubmed]
  4. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Hebrok, M., Kim, S.K., Melton, D.A. Genes Dev. (1998) [Pubmed]
  5. BMP4 plays a key role in left-right patterning in chick embryos by maintaining Sonic Hedgehog asymmetry. Monsoro-Burq, A., Le Douarin, N.M. Mol. Cell (2001) [Pubmed]
  6. Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes. Cordero, D., Marcucio, R., Hu, D., Gaffield, W., Tapadia, M., Helms, J.A. J. Clin. Invest. (2004) [Pubmed]
  7. Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH. Schneider, R.A., Hu, D., Rubenstein, J.L., Maden, M., Helms, J.A. Development (2001) [Pubmed]
  8. Shh and Fgf8 act synergistically to drive cartilage outgrowth during cranial development. Abzhanov, A., Tabin, C.J. Dev. Biol. (2004) [Pubmed]
  9. Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis. Charrier, J.B., Lapointe, F., Le Douarin, N.M., Teillet, M.A. Development (2001) [Pubmed]
  10. The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation. Grieshammer, U., Minowada, G., Pisenti, J.M., Abbott, U.K., Martin, G.R. Development (1996) [Pubmed]
  11. Sonic hedgehog and retinoic acid are not sufficient to induce motoneuron generation in the avian caudal neural tube. Afonso, N.D., Catala, M. Dev. Biol. (2005) [Pubmed]
  12. Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb. Duprez, D., Fournier-Thibault, C., Le Douarin, N. Development (1998) [Pubmed]
  13. Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear. Bok, J., Bronner-Fraser, M., Wu, D.K. Development (2005) [Pubmed]
  14. Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb. Duprez, D.M., Kostakopoulou, K., Francis-West, P.H., Tickle, C., Brickell, P.M. Development (1996) [Pubmed]
  15. Evidence for a role of protein kinase C in FGF signal transduction in the developing chick limb bud. Lu, H.C., Swindell, E.C., Sierralta, W.D., Eichele, G., Thaller, C. Development (2001) [Pubmed]
  16. Cloning and expression pattern of chicken Pitx2: a new component in the SHH signaling pathway controlling embryonic heart looping. St Amand, T.R., Ra, J., Zhang, Y., Hu, Y., Baber, S.I., Qiu, M., Chen, Y. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Developmental expression of chick twist and its regulation during limb patterning. Tavares, A.T., Izpisúja-Belmonte, J.C., Rodriguez-León, J. Int. J. Dev. Biol. (2001) [Pubmed]
 
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