Sanchez Moreno, C.; Badyaev, A.

Multicellular morphogenesis must balance organismal cohesion with local tissue differentiation. Migratory stem cells commonly fulfill these dual needs by orchestrating region-specific tissue differentiation, yet how they balance the maintenance of stemness with positional sensitivity is unclear. Here, we show that in the developing avian beak, early arriving neural crest-derived mesenchymal (NCM) cells transiently match protein profiles of the overlying epithelium, which diverges as development proceeds. This local mimicry phase propagates region-specific epithelial signaling into the mesenchyme, producing distinct boundaries that anchor mesenchymal cell condensations. As NCM cells accumulate, cells within condensations undergo morphological and molecular homogenization, erasing regional differences in protein expression and restoring cellular multipotency. These cycles of transient specialization and homogenization - driven by universal processes of cell proliferation and migration - enable NCM cells to reconcile location-specific anchoring signals with stemness needed for ongoing regional specification of growing beak. By balancing global coordination with local divergence, this developmental organization can facilitate the remarkable evolutionary diversification of avian beaks.