TY  - JOUR
A1  - Luck, Robert
A1  - Karakatsani, Andromachi
A1  - Shah, Bhavin
A1  - Schermann, Géza
A1  - Adler, Heike
A1  - Kupke, Janina
A1  - Tisch, Nathalie
A1  - Jeong, Hyun-Woo
A1  - Back, Michaela Kerstin
A1  - Hetsch, Florian
A1  - D'Errico, Anna
A1  - De Palma, Michele
A1  - Wiedtke, Ellen
A1  - Grimm, Dirk
A1  - Acker-Palmer, Amparo
A1  - Engelhardt, Jakob von
A1  - Adams, Ralf H.
A1  - Augustin, Hellmut
A1  - Ruiz de Almodóvar, Carmen
T1  - The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner
T2  - Cell reports
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.
KW  - Purkinje cell
KW  - cerebellum
KW  - neurodevelopment
KW  - neuro-vascular
KW  - angiogenesis
KW  - angipoietin
KW  - Tie2
KW  - blood vessels
KW  - dendritic morphology
KW  - dendritic branching
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63049
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-630495
SN  - 2211-1247
N1  - The authors gratefully acknowledge the data storage service SDS@hd supported by the Ministry of Science, Research and the Arts Baden-Württemberg (M.W.K.) and the German Research Foundation (DFG) through grant INST 35/1314-1 FUGG and INST 35/1503-1 FUGG. R.L. was supported by a Boehringer Ingelheim Fonds fellowship. This work was supported by the Schram Foundation and the Chica and Heinz Schaller Foundation, by research grants of the Deutsche Forschungsgemeinschaft (DFG) from FOR2325 (“Interactions at the Neurovascular Interface” [to C.R.d.A and R.H.A.]), by DFG grants from SFB1366 (“Vascular Control of Organ Function;” Project number 394046768-SFB 1366; [to C.R.d.A., R.H.A., and H.G.A.]), by funds from the Baden-Württemberg Stiftung special programme “Angioformatics Single Cell Platform” (to C.R.d.A. and to H.G.A.), and by the European Research Council Consolidator grant 864875 “OLI.VAS” (to C.R.d.A.) and ERC Advance Grant 787181 “Angiomature” (to H.G.A.).
VL  - 36
IS  - 7, art. 109522
SP  - 1
EP  - e7
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -