1. The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner.
- Author
-
Luck R, Karakatsani A, Shah B, Schermann G, Adler H, Kupke J, Tisch N, Jeong HW, Back MK, Hetsch F, D'Errico A, De Palma M, Wiedtke E, Grimm D, Acker-Palmer A, von Engelhardt J, Adams RH, Augustin HG, and Ruiz de Almodóvar C
- Subjects
- Angiopoietin-1 metabolism, Animals, Cerebellum blood supply, Cerebellum growth & development, Gene Deletion, Gene Expression Regulation, Integrases metabolism, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Models, Biological, Organ Specificity, Mice, Angiopoietin-2 metabolism, Dendrites metabolism, Morphogenesis, Purkinje Cells metabolism, Receptor, TIE-2 metabolism, Signal Transduction
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF