Université catholique de Louvain, Institute of Neuroscience, Developmental Neurobiology, Brussels, Belgium.
Université catholique de Louvain, Institute of Neuroscience, Mammalian Development and Cell Biology, Brussels, Belgium.
Mol Psychiatry. 2018 Mar;23(3):723-734. doi: 10.1038/mp.2017.236. Epub 2017 Dec 19.
The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.
大脑皮层的发育是一个受到严格调控的过程，依赖于内在和外在线索的精细协调作用。在这里，我们表明，前脑脑膜和顶端神经祖细胞（aNPC）之间的通讯对于皮质发育至关重要，而 aNPC 的基底隔室是该通讯过程的关键。我们发现，粘连 G 蛋白偶联受体家族的钙粘蛋白 Celsr1 控制着贴附脑膜的 aNPC 基底突起的分支，从而调节视黄酸（RA）依赖性神经发生。Celsr1 的功能丧失会导致终足数量减少，改变 RA 依赖性转录活性，并使 aNPC 向自我更新的方向倾斜，牺牲基底祖细胞和神经元的产生。突变皮层的神经元数量减少，Celsr1 突变小鼠表现出小头畸形和行为异常。我们的研究结果揭示了 Celsr1 蛋白和神经祖细胞的基底隔室在大脑皮层发育过程中命运决定中的重要作用。
