TY  - JOUR
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
TI  - The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner.
JO  - Cell reports
VL  - 36
IS  - 7
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2021-01884
SP  - 109522
PY  - 2021
N1  - DKFZ-ZMBH Alliance
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.
KW  - Purkinje cell (Other)
KW  - Tie2 (Other)
KW  - angiogenesis (Other)
KW  - angipoietin (Other)
KW  - blood vessels (Other)
KW  - cerebellum (Other)
KW  - dendritic branching (Other)
KW  - dendritic morphology (Other)
KW  - neuro-vascular (Other)
KW  - neurodevelopment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34407407
DO  - DOI:10.1016/j.celrep.2021.109522
UR  - https://inrepo02.dkfz.de/record/170294
ER  -