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Cdkn1c drives muscle differentiation through a positive feedback loop with Myod

Osborn, DP; Li, K; Hinits, Y; Hughes, SM (2011) Cdkn1c drives muscle differentiation through a positive feedback loop with Myod. DEVELOPMENTAL BIOLOGY, 350 (2). 464 - 475 (12). ISSN 0012-1606 https://doi.org/10.1016/j.ydbio.2010.12.010
SGUL Authors: Osborn, Daniel Peter Sayer

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Abstract

Differentiation often requires conversion of analogue signals to a stable binary output through positive feedback. Hedgehog (Hh) signalling promotes myogenesis in the vertebrate somite, in part by raising the activity of muscle regulatory factors (MRFs) of the Myod family above a threshold. Hh is known to enhance MRF expression. Here we show that Hh is also essential at a second step that increases Myod protein activity, permitting it to promote Myogenin expression. Hh acts by inducing expression of cdkn1c (p57Kip2) in slow muscle precursor cells, but neither Hh nor Cdkn1c is required for their cell cycle exit. Cdkn1c co-operates with Myod to drive differentiation of several early zebrafish muscle fibre types. Myod in turn up-regulates cdkn1c, thereby providing a positive feedback loop that switches myogenic cells to terminal differentiation.

Item Type: Article
Additional Information: PubMed ID: 21147088
Keywords: Animals, Cell Differentiation, Cyclin-Dependent Kinase Inhibitor p57, Feedback, Physiological, Hedgehog Proteins, Muscle Development, MyoD Protein, Myogenic Regulatory Factor 5, Myogenin, Signal Transduction, Zebrafish, Science & Technology, Life Sciences & Biomedicine, Developmental Biology, DEVELOPMENTAL BIOLOGY, Muscle, Cdkn1c, Zebrafish, Hedgehog, Myod, Myog, p57kip2, MYOGENIC REGULATORY FACTORS, ADULT SKELETAL-MUSCLE, CELL-CYCLE REGULATION, DOUBLE-MUTANT MICE, SONIC-HEDGEHOG, MOUSE DEVELOPMENT, SATELLITE CELLS, ZEBRAFISH, P57(KIP2), SLOW
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: DEVELOPMENTAL BIOLOGY
ISSN: 0012-1606
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Dates:
DateEvent
15 February 2011Published
Web of Science ID: WOS:000287117900020
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URI: http://openaccess.sgul.ac.uk/id/eprint/103280
Publisher's version: https://doi.org/10.1016/j.ydbio.2010.12.010

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