A fundamental question is how growth and patterning are timed during embryogenesis. Although it has been suggested that the cell cycle could be a timer, the underlying mechanisms remain elusive. Here we describe a cell cycle timer that operates in Sonic hedgehog (Shh)-expressing polarising region cells of the chick wing bud. Our data are consistent with Shh signalling stimulating polarising region cell proliferation via Cyclin D2, and then inhibiting proliferation via a Bmp2-p27kip1 pathway. When Shh signalling is blocked, polarising region cells over-proliferate and form an additional digit, which can be prevented by applying Bmp2 or by inhibiting D cyclin activity. In addition, Bmp2 also restores posterior digit identity in the absence of Shh signalling, thus indicating that it specifies antero-posterior (thumb to little finger) positional values. Our results reveal how an autoregulatory cell cycle timer integrates growth and specification and is widely applicable to many tissues.
Source data is provided for flow cytometry
- Joseph Pickering
- Kavitha Chinnaiya
- Matthew Towers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Marianne E Bronner, California Institute of Technology, United States
© 2019, Pickering et al.
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