Sharp cell type boundaries emerge from coordinated morphogen signaling [CUT&Run]

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 by reducing 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.