Sharp cell type boundaries emerge from coordinated morphogen signaling
13 affiliations
- 1Computational Biology and Biomedical Informatics Program, Yale University, New Haven, Connecticut 06520, USA
- 2Department of Pathology, Yale University, New Haven, Connecticut 06520, USA
- 3Department of Dermatology, Yale University, New Haven, Connecticut 06520, USA
- 4Molecular, Cellular, and Developmental Biology Program, Yale University, New Haven, Connecticut 06520, USA
- 5Department of Genetics, Yale University, New Haven, Connecticut 06520, USA
- 6The Jackson Laboratory, Bar Harbor, Maine 04609, USA
- 7School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA
- 8Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
- 9Medical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan 48105, USA
- 10Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York 10016, USA
- 11Department of Cell Biology, New York University Grossman School of Medicine, New York, New York 10016, USA
- 12Colon Cancer Project, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606-8501, Japan
- 13Department of Applied and Computational Mathematics, Yale University, New Haven, Connecticut 06511, USA
Abstract
Classic models of the French flag problem depict sharp cell type boundaries emerging from threshold responses to morphogen gradients. How discrete cell type boundaries arise from morphogen signals that vary continuously across developing tissues remains incompletely understood. We use hair follicle dermal condensate (DC) formation to study a sharp developmental transition in which proliferative progenitors undergo cell cycle exit concurrent with molecular differentiation. Using genetic and genomic approaches, we show that Wnt and Hedgehog signaling coordinate separable cellular events during DC commitment. Elevated Wnt signaling promotes cell cycle exit through reduced chromatin binding of the Hedgehog mediator GLI3, while Hedgehog signaling induces differentiation genes in a Wnt-dependent manner and simultaneously elevates Wnt activity. When these responses coincide, differentiation and cell cycle exit occur together, limiting the duration and abundance of intermediate states and producing a sharp boundary. When they do not, intermediate states persist and expand, producing a graded boundary. Thus, a sharp boundary can emerge from a continuous transition that is compressed in time and space.
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BibTeX
@misc{li2026sharp,
title = {{Sharp cell type boundaries emerge from coordinated morphogen signaling}},
author = {Ruiqi Li and Yiqun Jiang and Sarah Platt and Tianchi Xin and Shagun Lukkad and Sarah Van and Kevin A. Peterson and Ryan Driskell and Jonathan Zhu and Hainan Lam and Eva-LaRue Barber and David H. Wang and Chae Ho Lim and Makoto Mark Taketo and Yuval Kluger and Peggy Myung},
howpublished = {Genes \& Development},
year = {2026},
month = nov,
doi = {10.1101/gad.353815.126},
url = {https://doi.org/10.1101/gad.353815.126},
note = {CC BY-NC 4.0},
}
RIS
TY - UNPB
TI - Sharp cell type boundaries emerge from coordinated morphogen signaling
AU - Ruiqi Li
AU - Yiqun Jiang
AU - Sarah Platt
AU - Tianchi Xin
AU - Shagun Lukkad
AU - Sarah Van
AU - Kevin A. Peterson
AU - Ryan Driskell
AU - Jonathan Zhu
AU - Hainan Lam
AU - Eva-LaRue Barber
AU - David H. Wang
AU - Chae Ho Lim
AU - Makoto Mark Taketo
AU - Yuval Kluger
AU - Peggy Myung
PY - 2026
DA - 2026/11/01
PB - Genes & Development
DO - 10.1101/gad.353815.126
UR - https://doi.org/10.1101/gad.353815.126
AB - Classic models of the French flag problem depict sharp cell type boundaries emerging from threshold responses to morphogen gradients. How discrete cell type boundaries arise from morphogen signals that vary continuously across developing tissues remains incompletely understood. We use hair follicle dermal condensate (DC) formation to study a sharp developmental transition in which proliferative progenitors undergo cell cycle exit concurrent with molecular differentiation. Using genetic and genomic approaches, we show that Wnt and Hedgehog signaling coordinate separable cellular events during DC commitment. Elevated Wnt signaling promotes cell cycle exit through reduced chromatin binding of the Hedgehog mediator GLI3, while Hedgehog signaling induces differentiation genes in a Wnt-dependent manner and simultaneously elevates Wnt activity. When these responses coincide, differentiation and cell cycle exit occur together, limiting the duration and abundance of intermediate states and producing a sharp boundary. When they do not, intermediate states persist and expand, producing a graded boundary. Thus, a sharp boundary can emerge from a continuous transition that is compressed in time and space.
SN - 0890-9369
SN - 1549-5477
ER -