UC San Diego

Proper development of the nervous system requires strict regulation of neurogenesis. Neural progenitor cells are not only regulated by cell-autonomous genetic programs, but are also responsive to extracellular signals. In vitro evidence suggests that the vasculature may provide such regulatory cues. Although both adult and embryonic neural stem cells associate with blood vessels, vascular-mediated signaling pathways have only been identified for adult neurogenesis. Here, I provide in vivo characterization of the neurovascular niche during development, including potential mechanisms for vascular-mediated regulation of neurogenesis.

Radial glia, the neural progenitors during developmental neurogenesis, are typified by a long, radial process that terminates as an endfoot at the pial surface. Using in vivo time lapse imaging in Xenopus laevis, I demonstrate that a subset of radial glial endfeet closely appose the vasculature, and further, maintain this proximity over time. Even so, I found no correlation between vascular apposition and proliferative behavior. Clonal lineage analysis of 70 radial glia demonstrated that vascular apposition does not bias radial glia towards specific neurogenic events, which include asymmetric division, symmetric division, and direct differentiation. While this suggests that vascular apposition does not affect neurogenesis, it does not preclude the possibility that secreted vascular cues could regulate neurogenesis by signaling to nearby endfeet. Indeed, intracardial injection of fluorescent tracers showed that vascular-circulating molecules are endocytosed by radial glial endfeet, regardless of apposition to the vasculature. Finally, I tested two candidate signaling systems for effects on proliferation and differentiation, but did not find conclusive evidence for vascular-mediated regulation of neurogenesis. Together, these findings further describe interactions between neural progenitors and the vasculature, and identify unique features of the neurovascular niche during developmental neurogenesis.