A2: Role of the vasculature in shaping the developing central nervous system
Carmen Ruiz de Almodóvar
This project is focused on understanding the role of the vasculature as an orchestrator of neuronal development in the developing central nervous system (CNS). For this purpose, we will focus on the developing spinal cord and brain. We will use a combination of state of the art tissue clearing techniques, 3D imaging, to understand the tridimensional anatomical pattern and cellular correlation between the developing and ingressing vasculature and developing neurons in the CNS. We will combine the characterization of the dynamic gene expression profile and properties of endothelial cells within the developing CNS, with mouse genetics, biochemistry and cell biology methods to ultimately identify angiocrine-derived factors responsible for regulating the development of spinal cord, cortical and hippocampal neurons. This project will thus open new paths to further investigate and develop treatment for different developmental neuropathologies.
Schematic of neocortex development: Neuroepithelial cells mature into radial glial cells (RGCs-yellow) and proliferate symmetrically to self-generate. Asymmetric divisions give rise to either neurons (cyan) or basal progenitors (pink), which undergo final symmetric divisions to give rise to neurons. Nascent neurons initiate an axon first, either tangentially or ventrally, which is then followed by a leading process. Neurons undergo locomotion mode of migration using the support of RGC fibers and start occupying their positions. Cortical neurons undergo terminal translocation to position themselves in their final stages of migration.