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

• Published in: Cell reports (Cambridge) 2021-08, Vol.36 (7), p.109522-109522, Article 109522
• Main Authors: Luck, Robert, Karakatsani, Andromachi, Shah, Bhavin, Schermann, Geza, Adler, Heike, Kupke, Janina, Tisch, Nathalie, Jeong, Hyun-Woo, Back, Michaela Kerstin, Hetsch, Florian, D’Errico, Anna, De Palma, Michele, Wiedtke, Ellen, Grimm, Dirk, Acker-Palmer, Amparo, von Engelhardt, Jakob, Adams, Ralf H., Augustin, Hellmut G., Ruiz de Almodóvar, Carmen
• Format: Article
• Language: English
• Subjects: angiogenesis; Angiopoietin-1 - metabolism; Angiopoietin-2 - metabolism; angipoietin; Animals; blood vessels; cerebellum; Cerebellum - blood supply; Cerebellum - growth & development; Dendrites - metabolism; dendritic branching; dendritic morphology; Gene Deletion; Gene Expression Regulation; Integrases - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Biological; Morphogenesis; neuro-vascular; neurodevelopment; Organ Specificity; Purkinje cell; Purkinje Cells - metabolism; Receptor, TIE-2 - metabolism; Signal Transduction; Tie2
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109522

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. [Display omitted] •Ang1 and Ang2 are expressed in cerebellar neural and endothelial cells, respectively•The angiopoietin receptor Tie2 is expressed in blood vessels and Purkinje cells•Tie2 signaling regulates PC dendritic morphogenesis in a cell-autonomous manner•PCs network functionality is altered in PC specific Tie2-deficient mice Luck et al. describe a mechanism regulating Purkinje cell dendritic morphogenesis. They show that Tie2 signaling acts in a cell-autonomous manner in Purkinje cells. The ligands, Ang1 and Ang2, are expressed in neural and endothelial cells, respectively. This pathway is required for proper dendritic morphogenesis and neuronal functionality.