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A self-generated Toddler gradient guides mesodermal cell migration.

ABSTRACT: The sculpting of germ layers during gastrulation relies on the 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 a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. 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.

SUBMITTER: Stock J

PROVIDER: S-EPMC9473572 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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A self-generated Toddler gradient guides mesodermal cell migration.

Stock Jessica J Kazmar Tomas T Schlumm Friederike F Hannezo Edouard E Pauli Andrea A

Science advances 20220914 37

The sculpting of germ layers during gastrulation relies on the 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 a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is ...[more]

PMID: 36103529

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