Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California, 95064.
J Comp Neurol. 2014 Feb 1;522(2):372-92. doi: 10.1002/cne.23405.
Alternative splicing of pre-mRNAs can rapidly regulate the expression of large groups of proteins. The RNA binding protein TRA2B (SFRS10) plays well-established roles in developmentally regulated alternative splicing during Drosophila sexual differentiation. TRA2B is also essential for mammalian embryogenesis and is implicated in numerous human diseases. Precise regulation of alternative splicing is critical to the development and function of the central nervous system; however, the requirements for specific splicing factors in neurogenesis are poorly understood. This study focuses on the role of TRA2B in mammalian brain development. We show that, during murine cortical neurogenesis, TRA2B is expressed in both neural progenitors and cortical projection neurons. Using cortex-specific Tra2b mutant mice, we show that TRA2B depletion results in apoptosis of the neural progenitor cells as well as disorganization of the cortical plate. Thus, TRA2B is essential for proper development of the cerebral cortex.
前体 mRNA 的可变剪接可以快速调节大量蛋白质的表达。RNA 结合蛋白 TRA2B(SFRS10)在果蝇性分化过程中的发育调控可变剪接中发挥着成熟的作用。TRA2B 对于哺乳动物胚胎发生也是必不可少的,并且与许多人类疾病有关。可变剪接的精确调控对于中枢神经系统的发育和功能至关重要;然而,神经发生中特定剪接因子的要求知之甚少。本研究关注 TRA2B 在哺乳动物大脑发育中的作用。我们表明,在小鼠皮质神经发生过程中,TRA2B 在神经祖细胞和皮质投射神经元中均有表达。使用皮质特异性 Tra2b 突变小鼠,我们表明 TRA2B 的耗竭导致神经祖细胞凋亡和皮质板的紊乱。因此,TRA2B 对于大脑皮层的正常发育是必不可少的。