PRDM16 orchestrates angiogenesis via neural differentiation in the developing brain.,Cell Death and Differentiation

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PRDM16 orchestrates angiogenesis via neural differentiation in the developing brain.
Cell Death and Differentiation ( IF 13.7 ) Pub Date : 2020-02-03 , DOI: 10.1038/s41418-020-0504-5
Libo Su _{1,

2,

3} , Xuepei Lei _{1,

2,

3} , Hongyan Ma _{1,

4} , Chao Feng _{1,

2} , Jing Jiang ₅ , Jianwei Jiao _{1,

2,

3,

6}

Affiliation

Angiogenesis plays crucial roles in maintaining the complex operation of central nervous system (CNS) development. The architecture of communication between neurogenesis and angiogenesis is essential to maintain normal brain development and function. Hence, any disruption of neuron-vascular communications may lead to the pathophysiology of cerebrovascular diseases and blood-brain barrier (BBB) dysfunction. Here we demonstrate that neural differentiation and communication are required for vascular development. Regarding the cellular and molecular mechanism, our results show that PRDM16 activity determines the production of mature neurons and their specific positions in the neocortex. In the cortical plate (CP), aberrant neurons fail to secrete modular calcium-binding protein 1 (SMOC1), an important neuronal signal that participates in neurovascular communication to regulate CNS angiogenesis. Neuronal SMOC1 interacts with TGFBR1 by activating the transcription factors phospho-Smad2/3 to convey intercellular signals to endothelial cells (ECs) in the TGF-β-Smad signaling pathway. Together, our results highlight a crucial coordinated neurovascular development process orchestrated by PRDM16 and reveal the importance of intimate communication for building the neurovascular network during brain development.

中文翻译：

PRDM16 通过发育中的大脑中的神经分化来协调血管生成。

血管生成在维持中枢神经系统 (CNS) 发育的复杂运作中起着至关重要的作用。神经发生和血管发生之间的通讯结构对于维持正常的大脑发育和功能至关重要。因此，神经元血管通讯的任何中断都可能导致脑血管疾病和血脑屏障 (BBB) 功能障碍的病理生理学。在这里，我们证明了血管发育需要神经分化和交流。关于细胞和分子机制，我们的结果表明 PRDM16 活性决定了成熟神经元的产生及其在新皮质中的特定位置。在皮质板 (CP) 中，异常神经元无法分泌模块化钙结合蛋白 1 (SMOC1)，一种重要的神经元信号，参与神经血管通讯以调节 CNS 血管生成。神经元 SMOC1 通过激活转录因子 phospho-Smad2/3 与 TGFBR1 相互作用，从而在 TGF-β-Smad 信号通路中将细胞间信号传递给内皮细胞 (EC)。总之，我们的结果突出了由 PRDM16 精心策划的关键协调神经血管发育过程，并揭示了亲密交流对于在大脑发育过程中建立神经血管网络的重要性。

更新日期：2020-02-03

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