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

Publication date: 22 May 2017
Source:Developmental Cell, Volume 41, Issue 4
Author(s): Shang Ma, Devi Santhosh, Peeyush Kumar T., Zhen Huang
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-region-specific neural progenitor-based signaling pathway dedicated to regulating GM vessel development. This pathway consists of cell-surface sphingosine-1-phosphate receptors, an intracellular cascade including Gα co-factor Ric8a and p38 MAPK, and target gene integrin β8, which in turn regulates vascular TGF-β 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.

Graphical abstract

Teaser

Germinal matrix vessels in the brain are particularly fragile and prone to hemorrhage. Ma et al. uncover a neurovascular pathway specifically regulating germinal matrix vessel maturation, providing molecular-cellular insights and intervention venues.


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