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

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 ( )-expressing polarising region cells of the chi...

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Bibliographic Details
Published in:eLife 2019-09, Vol.8
Main Authors: Pickering, Joseph, Chinnaiya, Kavitha, Towers, Matthew
Format: Article
Language:English
Subjects:
Acids
Animal wings
Animals
Bone Morphogenetic Protein 2 - metabolism
Bone morphogenetic proteins
Cell Cycle
Cell growth
Cell Proliferation
Chick Embryo
Chicks (Infant chickens)
Cyclin D - metabolism
Cyclin D2
Cyclin-dependent kinase inhibitor p27
Developmental Biology
digits
Embryogenesis
Embryonic development
Ethanol
Gene expression
Gene Expression Regulation, Developmental
Genetic aspects
growth
Hedgehog protein
Hedgehog Proteins - metabolism
limb
patterning
Phase transitions
Physiological aspects
Shh
Signal Transduction
timing
Wings, Animal - embryology
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Summary: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 ( )-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-p27 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.47625