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Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish

ABSTRACT During gastrulation, endodermal cells actively migrate to the interior of the embryo, but the signals that initiate and coordinate this migration are poorly understood. By transplanting ectopically induced endodermal cells far from the normal location of endoderm specification, we identified the inputs that drive internalization without the confounding influences of fate specification and global morphogenic movements. We find that Nodal signaling triggers an autocrine circuit for initiating endodermal internalization. Activation of the Nodal receptor directs endodermal specification through sox32 and also induces expression of more Nodal ligands. These ligands act in an autocrine fashion to initiate endodermal cell sorting. Our work defines an ‘AND’ gate consisting of sox32-dependent endodermal specification and Nodal ligand reception controlling endodermal cell sorting to the inner layer of the embryo at the onset of gastrulation. Summary: In vivo transplantation studies demonstrate that both sox32-dependent endodermal specification and Nodal ligand reception are necessary to drive sorting of ectopic endodermal cells to the zebrafish inner layer.