Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms

One hundred years ago, Spemann and Mangold identified the organizer, a critical embryonic region that establishes vertebrate body axes by directing cell fate and morphogenesis. A conserved vertebrate mechanism involves the regulation of a ventral-to-dorsal BMP activity gradient during gastrulation by the organizer-expressed molecules. In zebrafish, BMP signaling controls mesodermal cell convergence and extension (C&E) by inhibiting Planar Cell Polarity (PCP) signaling and regulating cell adhesion. This allows lateral cells to converge toward the dorsal midline while directing ventral cells toward the tail bud. However, BMP's role in endodermal cell movements and the temporal precision of its regulatory functions remain poorly understood. Using optogenetics and other loss- and gain-of-function approaches, we investigated BMP's role in mesoderm and endoderm C&E. We found that low BMP signaling promotes extension in both germ layers, whereas high BMP signaling inhibits their C&E. Remarkably, BMP signaling activation for 1 h rapidly redirected dorsal to ventral migration of both mesodermal and endodermal cells. However, when BMP signaling was selectively elevated in endoderm in embryos with reduced BMP signaling, endoderm still mimicked mesodermal cell movements, indicating that endodermal responses to BMP are non-cell autonomous. We show that movements of endodermal cells in gastrulae with normal or elevated BMP signaling are not entirely dependent on mesoderm or the Cxcl12b/Cxcr4a GPCR pathway, suggesting additional mechanisms underlie endoderm C&E. Our findings highlight the critical role of the BMP morphogen gradient in coordinated C&E movements of mesodermal and endodermal cells. BMP employs both direct and indirect mechanisms to ensure robust embryonic patterning and morphogenesis of germ layers.