Open AccessOligodendrocyte precursor cell specification is regulated by bidirectional neural progenitor–endothelial cell crosstalk
Author(s) -
Isidora Paredes,
José Ricardo dos Santos Vieira,
Bhavin Shah,
Carla F Ramunno,
Julia Dyckow,
Heike Adler,
Melanie Richter,
Géza Schermann,
Evangelia Giannakouri,
Lucas Schirmer,
Hellmut G. Augustin,
Carmen Ruiz de Almodóvar
Publication year - 2021
Publication title -
nature neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.403
H-Index - 422
eISSN - 1546-1726
pISSN - 1097-6256
DOI - 10.1038/s41593-020-00788-z
Subject(s) - sonic hedgehog , crosstalk , neural stem cell , progenitor cell , precursor cell , microbiology and biotechnology , oligodendrocyte , biology , neuroscience , regulator , progenitor , endothelial stem cell , cell , signal transduction , stem cell , central nervous system , myelin , gene , in vitro , physics , biochemistry , optics , genetics
Neural-derived signals are crucial regulators of CNS vascularization. However, whether the vasculature responds to these signals by means of elongating and branching or in addition by building a feedback response to modulate neurodevelopmental processes remains unknown. In this study, we identified bidirectional crosstalk between the neural and the vascular compartment of the developing CNS required for oligodendrocyte precursor cell specification. Mechanistically, we show that neural progenitor cells (NPCs) express angiopoietin-1 (Ang1) and that this expression is regulated by Sonic hedgehog. We demonstrate that NPC-derived Ang1 signals to its receptor, Tie2, on endothelial cells to induce the production of transforming growth factor beta 1 (TGFβ1). Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward oligodendrocyte precursor cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis.