Department of Biology and Center for Cell Reprogramming, Georgetown University, Washington, DC 20057.
Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20057.
eNeuro. 2020 Jan 22;7(1). doi: 10.1523/ENEURO.0270-19.2019. Print 2020 Jan/Feb.
Myelination of the CNS relies on the production and differentiation of oligodendrocyte (OL) precursor cells (OPCs) into mature OLs. During the first month of postnatal life, OPCs that populate the corpus callosum (CC) arise from neural stem cells (NSCs) in the subcallosal subventricular zone (SVZ), and then differentiate to generate myelinating OLs. However, the signals that regulate these processes are not fully understood. In this study, we show that endogenous expression of the retinoic acid (RA)-synthesizing enzyme retinaldehyde dehydrogenase 2 (RALDH2) is required for OPC generation and differentiation in the postnatal subcortical white matter. In male and female pups, conditional deletion of reduced OPC numbers and differentiation. Moreover, decreased OPC numbers coincided with reductions in NSC survival and expression of the sonic hedgehog (SHH) signaling effector protein in the SVZ. Additionally, GFAP expression in the CC was decreased, and cortical neuron numbers were altered. Our work suggests a role for endogenous RALDH2-dependent RA synthesis in OPC production and differentiation in the CC, as well as in the development of other cell types derived from NSCs in the embryonic ventricular zone (VZ) and SVZ, as well as the postnatal subcallosal SVZ.
中枢神经系统的髓鞘形成依赖于少突胶质细胞（OL）前体细胞（OPC）向成熟 OL 的产生和分化。在出生后的第一个月，位于胼胝体（CC）的 OPC 来源于侧脑室下区（SVZ）的神经干细胞（NSC），然后分化产生髓鞘形成的 OL。然而，调节这些过程的信号还不完全清楚。在这项研究中，我们表明，内源性表达视黄酸（RA）合成酶视黄醛脱氢酶 2（RALDH2）对于出生后皮质下白质中的 OPC 产生和分化是必需的。在雄性和雌性幼崽中，条件性缺失 会减少 OPC 数量并阻止其分化。此外，OPC 数量的减少与 SVZ 中 NSC 存活和 sonic hedgehog（SHH）信号效应蛋白 表达的减少相吻合。此外，CC 中的 GFAP 表达减少，皮质神经元数量发生改变。我们的工作表明，内源性 RALDH2 依赖性 RA 合成在 CC 中 OPC 的产生和分化，以及胚胎脑室区（VZ）和 SVZ 以及出生后侧脑室下 SVZ 中源自 NSC 的其他细胞类型的发育中发挥作用。
