Abstract

<h3>ABSTRACT</h3> The sculpting of germ layers during gastrulation relies on coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by the uniformly expressed and secreted protein Toddler/ELABELA/Apela, acting as a self-generated gradient. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor-based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo. <h3>One sentence summary</h3> Aplnr has a dual role to self-generate and sense a Toddler gradient directing mesodermal cells during zebrafish gastrulation.

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