Dr. Barbara Di Marco
Department of Clinical Neurobiology, German Cancer Research Center (DKFZ)
Seminar: “Functional Interaction Between Vascular Filopodia and Neural Stem Cells in the Developing Brain “.
Neurogenesis and angiogenesis are coordinated during embryonic brain development, and a proper interaction between these two processes is crucial for normal brain function. In our study, we investigate how neural stem cells (NSCs) and nascent blood vessels interplay in the ventricular zone (VZ) of ventral telencephalon, the embryonic brain area that gives rise to adult neural stem cells and GABAergic neurons. We show that nascent vessels contact dividing NSCs via endothelial filopodia in the apical VZ of the mouse and human ventral telencephalon. Using mouse vascular mutants, we show that an increase in the vascular filopodia density leads to increased number of mitotic apical NSCs, to apical NSC cell cycle delay, and favors early neuronal differentiation. Pharmacological experiments reveal that NSCs, in turn, induce vascular filopodia formation by overexpressing vascular endothelial growth factor (VEGF)–A while undergoing mitosis. This cellular contact between endothelial and neural cells works as a coordinated system to adjust the balance between NSC expansion and differentiation. Our results reveal an unexplored function of vascular filopodia on regulating neural stem cell activity and reveal that a reciprocal interaction between NSCs and vascular filopodia is fundamental during embryonic neurogenesis.
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