6533b7d8fe1ef96bd126aef4

RESEARCH PRODUCT

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

Dirk GrimmFlorian HetschJanina KupkeAnna D'erricoRalf H. AdamsAndromachi KarakatsaniHellmut G. AugustinHellmut G. AugustinHyun-woo JeongGéza SchermannMichaela K BackHeike AdlerMichele De PalmaEllen WiedtkeRobert LuckJakob Von EngelhardtAmparo Acker-palmerCarmen Ruiz De AlmodovarNathalie TischBhavin Shah

subject

CerebellumalphaCytoskeleton organizationAngiogenesisPurkinje cellprotocadherinsMorphogenesisneural progenitor cellsMice Transgenicself-avoidanceBiologyModels BiologicalGeneral Biochemistry Genetics and Molecular BiologyAngiopoietinAngiopoietin-2Purkinje Cellsddc:570CerebellumexpressionGene expressionmedicineAngiopoietin-1MorphogenesisAnimalsmouseMice KnockoutIntegrasessubventricular zonedifferentiationDendritesmtorc2Angiopoietin receptorReceptor TIE-2Cell biologyMice Inbred C57BLmedicine.anatomical_structuremessenger-rnaGene Expression RegulationOrgan Specificityembryonic structurescardiovascular systembiology.proteinGene DeletionSignal Transduction

description

Neuro-vascular communication is essential to synchronize central nervous system development. Here, we identify angiopoietin/Tie2 as a neuro-vascular signaling axis involved in regulating dendritic morphogenesis of Purkinje cells (PCs). We show that in the developing cerebellum Tie2 expression is not restricted to blood vessels, but it is also present 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, mice with deletion of Tie2 in PCs present alterations in PC network functionality. Altogether, our data propose Ang/Tie2 signaling as a mediator of intercellular communication between neural cells, ECs, and PCs, required for proper PC dendritic morphogenesis and function.

yearjournalcountryeditionlanguage
2021-08-01Cell reports
10.1016/j.celrep.2021.109522https://pubmed.ncbi.nlm.nih.gov/34407407