A Brain-Region-Specific Neural Pathway Regulating Germinal Matrix Angiogenesis

作者：Ma Shang; Santhosh Devi; Kumar Peeyush T; Huang Zhen^*

来源：Developmental Cell, 2017, 41(4): 366-+.

DOI：10.1016/j.devcel.2017.04.014

Intimate communication between neural and vascular cells is critical for normal brain development and function. Germinal matrix (GM), a key primordium for the brain reward circuitry, is unique among brain regions for its distinct pace of angiogenesis and selective vulnerability to hemorrhage during development. A major neonatal condition, GM hemorrhage can lead to cerebral palsy, hydrocephalus, and mental retardation. Here we identify a brain-regionspecific neural progenitor-based signaling pathway dedicated to regulating GM vessel development. This pathway consists of cell-surface sphingosine1- phosphate receptors, an intracellular cascade including G alpha co-factor Ric8a and p38 MAPK, and target gene integrin beta 8, which in turn regulates vascular TGF-beta signaling. These findings provide insights into region-specific specialization of neurovascular communication, with special implications for deciphering potent early-life endocrine, as well as potential gut microbiota impacts on brain reward circuitry. They also identify tissue-specific molecular targets for GM hemorrhage intervention.

• 出版日期2017-5-22