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

  • 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.
Author:Robert Luck, Andromachi Karakatsani, Bhavin Shah, Géza Schermann, Heike Adler, Janina Kupke, Nathalie Tisch, Hyun-Woo Jeong, Michaela Kerstin Back, Florian Hetsch, Anna D’Errico, Michele De Palma, Ellen Wiedtke, Dirk Grimm, Amparo Acker-PalmerORCiDGND, Jakob von Engelhardt, Ralf H. AdamsORCiD, Hellmut Augustin, Carmen Ruiz de Almodóvar
Parent Title (English):Cell reports
Publisher:Cell Press
Place of publication:Maryland Heights, MO
Document Type:Article
Date of Publication (online):2021/08/17
Date of first Publication:2021/08/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/05/18
Tag:Purkinje cell; Tie2; angiogenesis; angipoietin; blood vessels; cerebellum; dendritic branching; dendritic morphology; neuro-vascular; neurodevelopment
Issue:7, art. 109522
Page Number:23
First Page:1
Last Page:e7
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.).
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0