Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis

Mostafa Bakhti, Aimée Bastidas-Ponce, Sophie Tritschler, Oliver Czarnecki, Marta Tarquis-Medina, Eva Nedvedova, Jessica Jaki, Stefanie J. Willmann, Katharina Scheibner, Perla Cota, Ciro Salinno, Karsten Boldt, Nicola Horn, Marius Ueffing, Ingo Burtscher, Fabian J. Theis, Ünal Coskun, Heiko Lickert

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

During pancreas development endocrine cells leave the ductal epithelium to form the islets of Langerhans, but the morphogenetic mechanisms are incompletely understood. Here, we identify the Ca2+-independent atypical Synaptotagmin-13 (Syt13) as a key regulator of endocrine cell egression and islet formation. We detect specific upregulation of the Syt13 gene and encoded protein in endocrine precursors and the respective lineage during islet formation. The Syt13 protein is localized to the apical membrane of endocrine precursors and to the front domain of egressing endocrine cells, marking a previously unidentified apical-basal to front-rear repolarization during endocrine precursor cell egression. Knockout of Syt13 impairs endocrine cell egression and skews the α-to-β-cell ratio. Mechanistically, Syt13 is a vesicle trafficking protein, transported via the microtubule cytoskeleton, and interacts with phosphatidylinositol phospholipids for polarized localization. By internalizing a subset of plasma membrane proteins at the front domain, including α6β4 integrins, Syt13 modulates cell-matrix adhesion and allows efficient endocrine cell egression. Altogether, these findings uncover an unexpected role for Syt13 as a morphogenetic driver of endocrinogenesis and islet formation.

Original languageEnglish
Article number4540
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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