Coupling of cell proliferation to the segmentation clock promotes robust somite scaling
Year: 2026
Type: article
Abstract: How developing tissues coordinate growth and patterning to maintain their proportions remains unclear. During vertebrate somitogenesis, somite size scales with the presomitic mesoderm (PSM), where morphogen gradients and oscillating Notch, Wnt (wingless and Int-1), and fibroblast growth factor (FGF) signaling regulate segmentation. We find that proliferation is uniformly distributed throughout the oscillating PSM and, using long-term single-cell tracking and microfluidic entrainment in mouse embryo tails, provide evidence for functional coupling between cell-cycle progression and the segmentation clock, likely involving periodic cyclin D1 regulation among other mechanisms. A minimal model suggests that this coupling promotes uniform PSM growth and morphogen dilution, supporting robust somite formation. Loss of clock function increases Mesp2 patterning irregularity, whereas inhibiting proliferation alters morphogen profiles and somite scaling. Human in vitro somitogenesis models show a comparable clock-cell-cycle phase relationship, suggesting conservation across species. Together, these findings link clock-coupled proliferation to coordinated tissue growth, robust patterning, and scaling.
Source: Developmental Cell
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: National Science Foundation, Wellcome Trust, Royal Society, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, European Research Council, Kavli Institute for Theoretical Physics, University of California, Santa Barbara, RIKEN Center for Biosystems Dynamics Research, H2020 European Research Council
Awards: An inverted light-sheet microscope for the functional investigation of signalling dynamics during development and tissue homeostasis at single cell resolution, G5261598906, Signaling dynamics in the control of cell proliferation and differentiation during development and homeostasis, Kavli Institute for Theoretical Physics, G985207216
OpenAlex ID: W4406279012
