Graham Victoria, Khudyakov Jane, Ellis Pamela, Pevny Larysa
Neuroscience Center, Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Neuron. 2003 Aug 28;39(5):749-65. doi: 10.1016/s0896-6273(03)00497-5.
Neural progenitors of the vertebrate CNS are defined by generic cellular characteristics, including their pseudoepithelial morphology and their ability to divide and differentiate. SOXB1 transcription factors, including the three closely related genes Sox1, Sox2, and Sox3, universally mark neural progenitor and stem cells throughout the vertebrate CNS. We show here that constitutive expression of SOX2 inhibits neuronal differentiation and results in the maintenance of progenitor characteristics. Conversely, inhibition of SOX2 signaling results in the delamination of neural progenitor cells from the ventricular zone and exit from cell cycle, which is associated with a loss of progenitor markers and the onset of early neuronal differentiation markers. The phenotype elicited by inhibition of SOX2 signaling can be rescued by coexpression of SOX1, providing evidence for redundant SOXB1 function in CNS progenitors. Taken together, these data indicate that SOXB1 signaling is both necessary and sufficient to maintain panneural properties of neural progenitor cells.
脊椎动物中枢神经系统（CNS）的神经祖细胞由一般的细胞特征所定义，包括其假复层上皮形态以及分裂和分化能力。SOXB1转录因子，包括三个密切相关的基因Sox1、Sox2和Sox3，在整个脊椎动物中枢神经系统中普遍标记神经祖细胞和干细胞。我们在此表明，SOX2的组成型表达抑制神经元分化并导致祖细胞特征的维持。相反，SOX2信号传导的抑制导致神经祖细胞从脑室区脱离并退出细胞周期，这与祖细胞标志物的丧失和早期神经元分化标志物的出现有关。通过共表达SOX1可以挽救由抑制SOX2信号传导引起的表型，这为中枢神经系统祖细胞中SOXB1功能的冗余提供了证据。综上所述，这些数据表明SOXB1信号传导对于维持神经祖细胞的全神经特性既是必要的也是充分的。
