Spatiotemporally Dependent Vascularization Is Differently Utilized among Neural Progenitor Subtypes during Neocortical Development

Abstract

Summary: To facilitate efficient oxygen and nutrient delivery, blood vessels in the brain form three-dimensional patterns. However, little is known about how blood vessels develop stereographically in the neocortex and how they control the expansion and differentiation of neural progenitors during neocortical development. We show that highly vascularized and avascular regions are strictly controlled in a spatially and temporally restricted manner and are associated with distinct cell populations. Dividing basal progenitors and oligodendrocyte precursors preferentially contact honeycomb vessels, but dividing apical progenitors are localized in avascular regions without Flt1-positive endothelial cells but directly contact with sprouting neovascular tip cells. Therefore, not all blood vessels are associated equally with neural progenitors. Furthermore, a disruption of normal vascular patterning can induce abnormalities in neural development, whereas the impaired features of neural progenitors influenced angiogenesis patterning. These results indicate that close association between the nervous and vascular systems is essential for neocortex assembly. : Komabayashi-Suzuki et al. show that regional angiogenesis establishes separate neovascular hypoxic and perivascular niches in the developing neocortex. These niches are utilized by distinct progenitor cell types to achieve proper expansion, lineage specification, and differentiation of neocortical progenitor cells. Keywords: developing neocortex, stem cell niche, neural progenitors, angiogenesis, neurogenesis, VEGF, neural development, differentiation, neural stem cells, oligodendrocyte precursor cells