A multi-tiered mechanical mechanism shapes the early neural plate.

The formation of complex tissues during embryonic development requires an intricate spatiotemporal coordination of local mechanical processes regulating global tissue morphogenesis. Here, we uncover a novel mechanism that mechanically regulates the shape of the anterior neural plate (ANP), a vital forebrain precursor, during zebrafish gastrulation. Combining in vivo and in silico approaches we reveal that the ANP is shaped by global tissue flows regulated by distinct force-generating processes. We show that mesendoderm migration and E-cadherin-dependent differential tissue interactions control distinct flow regimes in the neuroectoderm. Initial opposing flows lead to neuroectoderm cell internalisation and progressive multilayer tissue folding which in turn provide forces driving ANP tissue reshaping. We find that convergent extension is dispensable for internalisation but required for ANP tissue extension. Our results highlight how spatiotemporal regulation and coupling of different mechanical processes between tissues in the embryo control the first internalisation and folding events of the developing brain.