Vue Tou Yia, Kim Euiseok J, Parras Carlos M, Guillemot Francois, Johnson Jane E
Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
Development. 2014 Oct;141(19):3721-31. doi: 10.1242/dev.105270. Epub 2014 Sep 5.
Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.
神经胶质细胞构成了哺乳动物中枢神经系统中的大多数细胞，对神经功能至关重要。然而，目前对神经胶质细胞发育的分子调控仍不完全清楚。我们发现，转录因子Ascl1（Mash1），其在神经发生中的作用最为人所知，在胚胎后期小鼠脊髓中产生的星形胶质细胞和少突胶质细胞谱系中也发挥作用。体内克隆命运图谱揭示了表达Ascl1的神经胶质祖细胞的异质性，并表明Ascl1定义了那些作为星形胶质细胞或少突胶质细胞局限于灰质（GM）或白质（WM）的细胞。神经发生后条件性删除Ascl1表明，在少突胶质细胞生成过程中，Ascl1是生成正确数量的白质少突胶质细胞前体细胞所必需的，但对灰质少突胶质细胞前体细胞并非如此，而在星形胶质细胞生成过程中，Ascl1在平衡背侧灰质原浆性星形胶质细胞与背侧白质纤维性星形胶质细胞数量方面发挥作用。因此，除了在神经发生中的功能外，Ascl1还标记神经胶质祖细胞，并控制脊髓灰质和白质中星形胶质细胞和少突胶质细胞的数量及分布。
