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The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner

ABSTRACT: Neuro-vascular communication is essential to synchronize central nervous system development. Yet, the specific cellular players, defined developmental processes and molecular mechanisms involved in this crosstalk remain poorly characterized. Here we identify the angiopoietin/Tie2 signaling axis as a crucial regulator of dendritic morphogenesis of Purkinje cells (PC) during cerebellum development. We show that in the developing cerebellum Tie2 expression is not restricted to blood vessels but it is also in PCs. Its ligands angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are expressed in neural cells and endothelial cells (ECs), respectively. PC-specific deletion of Tie2 results in reduced dendritic arborization, which is recapitulated in neural-specific Ang1-knockout and Ang2 full-knockout mice. Mechanistically, RNA sequencing reveals that Tie2 deficient PCs present alterations in gene expression of multiple genes involved in cytoskeleton organization, dendritic formation, growth and branching. Functionally, those morphological changes are accompanied by alterations in PC network electrophysiology. Altogether, our data propose that the Ang/Tie2 signaling axis serve as mediator of intercellular communication between neural cells, ECs and PCs, required to regulate PC dendritic morphogenesis and function.

ORGANISM(S): Mus musculus

PROVIDER: GSE178659 | GEO | 2021/12/31

REPOSITORIES: GEO

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