Fundación Instituto Leloir and Consejo Nacional de Investigaciones Científicas y Técnicas (IIBBA-CONICET), Buenos Aires 1405, Argentina.
Instituto de Investigación en Biomedicina de Buenos Aires, Partner Institute of the Max Planck Society (IBioBA-CONICET), Buenos Aires, Argentina.
Cell Rep. 2019 Aug 27;28(9):2264-2274.e3. doi: 10.1016/j.celrep.2019.07.087.
Generation of neuronal types at the right time, location, and number is essential for building a functional nervous system. Significant progress has been reached in understanding the mechanisms that govern neuronal diversity. Cerebrospinal fluid-contacting neurons (CSF-cNs), an intriguing spinal cord central canal population, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how CSF-cNs are specified after the neurogenesis-to-gliogenesis switch. Here, we identify delayed Ascl1 expression in mouse spinal progenitors during the gliogenic phase as key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and nonneuronal composition of the spinal central canal.
在正确的时间、地点和数量产生神经元类型对于构建功能正常的神经系统至关重要。在理解控制神经元多样性的机制方面已经取得了重大进展。脑脊液接触神经元（CSF-cNs）是脊髓中央管中的一个有趣群体，它们在神经发生向神经胶质发生转变之后的发育晚期与神经胶质细胞和室管膜细胞同时产生。目前尚不清楚 CSF-cNs 在神经发生向神经胶质发生转变之后是如何被特化的。在这里，我们发现小鼠脊髓祖细胞在神经胶质发生阶段中 Ascl1 的表达延迟，这是 CSF-cN 分化的关键。通过命运图谱和时间控制的缺失实验，我们证明 CSF-cNs 来源于表达 Ascl1 的细胞，并且 Ascl1 在羊膜动物脊髓中引发晚期神经发生。Ascl1 的缺失会将潜在的 CSF-cN 祖细胞转化为室管膜细胞。这些结果表明，晚期脊髓祖细胞具有产生神经元的潜力，并且 Ascl1 启动 CSF-cN 分化，控制脊髓中央管中神经元和非神经元的确切组成。
