TY - JOUR
T1 - The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner
AU - Luck, Robert
AU - Karakatsani, Andromachi
AU - Shah, Bhavin
AU - Schermann, Geza
AU - Adler, Heike
AU - Kupke, Janina
AU - Tisch, Nathalie
AU - Jeong, Hyun-Woo
AU - Back, Michaela Kerstin
AU - Hetsch, Florian
AU - D'Errico, Anna
AU - De Palma, Michele
AU - Wiedtke, Ellen
AU - Grimm, Dirk
AU - Acker-Palmer, Amparo
AU - von Engelhardt, Jakob
AU - Adams, Ralf H.
AU - Augustin, Hellmut G.
AU - Ruiz de Almodóvar, Carmen
PY - 2021/8/17
Y1 - 2021/8/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85112801582&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2021.109522
DO - 10.1016/j.celrep.2021.109522
M3 - Article
SN - 2211-1247
VL - 36
JO - Cell Reports
JF - Cell Reports
IS - 7
M1 - 109522
ER -