An autoregulatory cell cycle timer integrates growth and specification in chick wing digit development

• Main Authors: Joseph Pickering, Kavitha Chinnaiya, Matthew Towers
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-09-01
• Series: eLife
• Subjects: limb; patterning; growth; timing; Shh; digits
• Online Access: https://elifesciences.org/articles/47625

A fundamental question is how proliferation and growth 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 are widely applicable to many tissues.