Astrocytes control the development of the migration-promoting vasculature scaffold in the postnatal brain via VEGF signaling.
New neurons are constantly being generated in the postnatal subventricular zone. They have to migrate long distances via the rostral migratory stream (RMS) to reach their final destination in the olfactory bulb (OB). In adults, these neuronal precursors migrate in chains, ensheathed by astrocytic processes, and travel toward the OB along blood vessels (BVs) that topographically outline the RMS. The molecular and cellular mechanisms leading to the development of the RMS and the formation of the migration-promoting vasculature scaffold in the adult mice remain unclear. We now reveal that astrocytes orchestrate the formation and structural reorganization of the vasculature scaffold in the RMS and, during early developmental stages, the RMS contains only a few BVs oriented randomly with respect to the migrating neuroblasts. The first parallel BVs appeared at the outer border of the RMS, where vascular endothelial growth factor (VEGF)-expressing astrocytes are located. Gain-of-function and loss-of-function experiments revealed that astrocyte-derived VEGF plays a crucial role in the formation and growth of new BVs. Real-time videoimaging also showed that the migration of neuronal precursors in the developing RMS differs substantially from neuronal displacement in the adult migratory stream partially because of not yet fully developed vasculature scaffold. The downregulation of VEGF in vivo, specifically in the astrocytes of the developing RMS, affected the development of the vasculature scaffold and led to alterations in neuroblast migration. Altogether, our results demonstrate that astrocytes orchestrate the formation and growth of parallel BVs, crucial migration-promoting scaffolds in the adult migratory stream, via VEGF signaling.
Cellular Neurobiology Unit, Centre de Recherche Université Laval Robert-Giffard, Quebec City, Quebec, Canada G1J 2G3.
Lusine
L
Bozoyan
Jivan
J
Khlghatyan
Armen
A
Saghatelyan
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000254:growth & development*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018920:Coculture Techniques; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse