a functional requirement for astroglia in promoting blood vessel development in the early postnatal brain星形神经胶质的功能性需求促进血管发展在产后早期大脑.pdfVIP

A Functional Requirement for Astroglia in Promoting Blood Vessel Development in the Early Postnatal Brain 1,2 1,3 1 Shang Ma , Hyo Jun Kwon , Zhen Huang * 1 Departments of Neurology and Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 2 Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 3 Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin, United States of America Abstract Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net d