A cross-tissue physicochemical causal chain underlying vertebrate mandibular morphogenesis.

Understanding morphogenesis increasingly requires attention to physical aspects. In complex embryonic structures comprising multiple adjacent tissues, morphogenetic change in one tissue can impose geometric constraints that shape another tissue. However, such cross-tissue physical coordination remains largely unexplored. Using zebrafish jaw development, we show that dynamic folding of the oral ectoderm drives the elongation and fusion of mandibular primordia by constraining and guiding mesenchymal cell motion. This folding is initiated by Shh signaling, mainly from the adjacent neural tube, which establishes polarized behaviors in oral ectodermal cells. Notably, this phase of mandibular formation proceeds independently of cell proliferation and relies on polarized motion of both epithelium and mesenchyme. Our findings identify a physicochemical causal chain, offering a holistic view of complex embryonic tissue shaping.