Developmental Signals - Sonic hedgehog
(SHH) A secreted growth factor that binds patched (ptc) receptor on cell membrane. This protein has many different functions in different tissues of the developing embryo, the main role would be of establishing "pattern". SHH name derives from homology to the original fruitfly (drosophila) "hedgehog" mutation, where these flies have hairs located in regions (ventral) which are normally hair-free, and therefore have a disrupted body pattern.
Sonic Hedgehog (SHH) was isolated by homology to the Hh gene. SHH is a true signaling switch used in differentiating subpopulations of cells throughout the embryo. Depending on where the signal is being secreted, how far away the responsive cell population is and how SHH is proteolytically cleaved, will determine SHH function. SHH binds to the membrane receptors Patched (ptc) and BOC/CDON.
Nomenclature note lower case shh for other species, upper case SHH in humans.
Some Recent Findings
- Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. Butterfield NC, Metzis V, McGlinn E, Bruce SJ, Wainwright BJ, Wicking C. Development. 2009 Oct;136(20):3515-24. PMID: 19783740
- Zhu J, Nakamura E, Nguyen MT, Bao X, Akiyama H, Mackem S. Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud. Dev Cell. 2008 Apr;14(4):624-32. PMID: 18410737
- "One of the first changes we noted was that the dorsoventral polarity of the forebrain was disturbed, which manifested as a loss of Shh in the ventral telencephalon, a reduction in expression of the ventral markers Nkx2.1 and Dlx2, and a concomitant expansion of the dorsal marker Pax6. In addition to changes in the forebrain neuroectoderm, we observed altered gene expression patterns in the facial ectoderm. For example, Shh was not induced in the frontonasal ectoderm, and Ptc and Gli1 were reduced in both the ectoderm and adjacent mesenchyme."
- Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008 Apr;40(4):403-10. PMID: 18327258
- Sun M, Ma F, Zeng X, Liu Q, Zhao XL, Wu FX, Wu GP, Zhang ZF, Gu B, Zhao YF, Tian SH, Lin B, Kong XY, Zhang XL, Yang W, Lo W, Zhang X. Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long-range, limb-specific SHH enhancer. J Med Genet. 2008 Apr 16 PMID: 18417549
- Chamberlain CE, Jeong J, Guo C, Allen BL, McMahon AP. Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning. Development. 2008 Mar;135(6):1097-106. PMID: 18272593
Developmental patterning signal.
SHH is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons.
- neural crest cell survival in the foregut endoderm of jaw development PNAS
SHH is secreted by the zone of polarizing activity (ZPA) organizing limb axis formation.
SHH is secreted by the forebrain neuroectoderm and the facial ectoderm for upper face and nasofrontal bud development. PMID: 15979605
SHH has still others roles in organ development in lung, pancreas.
The secreted protein binds to the cell surface membrane protein the patched receptor (ptc).
- UNSW Embryology - Molecular Factors - sonic hedgehog | Molecular Notes | Musculoskeletal Notes | Neural Notes
- OMIM - SONIC HEDGEHOG
Cite this page: Hill, M.A. (2019, September 20) Embryology Developmental Signals - Sonic hedgehog. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Sonic_hedgehog
- © Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G