Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock

Kavitha Chinnaiya, Cheryll Tickle and Matthew Towers ()
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Kavitha Chinnaiya: MRC Centre for Developmental and Biomedical Genetics, University of Sheffield
Cheryll Tickle: University of Bath, Claverton Down Road
Matthew Towers: MRC Centre for Developmental and Biomedical Genetics, University of Sheffield

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: Abstract How time is measured is an enduring issue in developmental biology. Classical models of somitogenesis and limb development implicated intrinsic cell cycle clocks, but their existence remains controversial. Here we show that an intrinsic cell cycle clock in polarizing region cells of the chick limb bud times the duration of Sonic hedgehog (Shh) expression, which encodes the morphogen specifying digit pattern across the antero-posterior axis (thumb to little finger). Timing by this clock starts when polarizing region cells fall out of range of retinoic acid signalling. We found that timing of Shh transcription by the cell cycle clock can be reset, thus revealing an embryonic form of self-renewal. In contrast, antero-posterior positional values cannot be reset, suggesting that this may be an important constraint on digit regeneration. Our findings provide the first evidence for an intrinsic cell cycle timer controlling duration and patterning activity of a major embryonic signalling centre.

Date: 2014
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DOI: 10.1038/ncomms5230

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