A Brain-Region-Specific Neural Pathway Regulating Germinal Matrix Angiogenesis.
A Brain-Region-Specific Neural Pathway Regulating Germinal Matrix Angiogenesis.
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DOI：
10.1016/j.devcel.2017.04.014
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发表时间：
2017-05-22
影响因子：
11.8
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Ma S;Santhosh D;Kumar T P;Huang Z
神经细胞和血管细胞之间的密切交流对大脑的正常发育和功能至关重要。生发基质（Germinal matrix， GM）是大脑奖赏回路的关键原基，在大脑区域中具有独特的血管生成速度和发育过程中对出血的选择性易感性。GM出血是一种主要的新生儿疾病，可导致脑瘫、脑积水和智力迟钝。在这里，我们确定了一个专门调节GM血管发育的脑区域特异性神经祖细胞信号通路。该通路由细胞表面鞘氨醇-1-磷酸受体、包括Gα辅助因子Ric8a和p38 MAPK在内的细胞内级联以及靶基因整合素β8组成，后者反过来调节血管tgf - β信号传导。这些发现为神经血管通讯的区域特异性专业化提供了新的见解，对破译早期生命内分泌以及肠道微生物群对大脑奖励回路的潜在影响具有特殊意义。他们还确定了GM出血干预的组织特异性分子靶点。脑内的生发基质血管特别脆弱，容易出血。Ma等人发现了一种特异性调节生发基质血管成熟的神经血管通路，提供了新的分子细胞见解和干预场所。
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 TGFβ signaling. These findings provide novel 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. 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 novel molecular-cellular insights and intervention venues.