缺口信号在发育中的背前脑中调节神经元到寡细胞开关方面发挥着双重作用
Luuli N Tran1,2, Sarah K Loew1,3, Santos J Franco4,2,3,5
1Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
概括
痕信号精确地控制发育中的大脑中的寡类细胞生产时间. 适当的Notch平衡至关重要,因为抑制和过度激活都会扰乱寡细胞的生成,突出显示其在神经发育中的复杂作用.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 脊前脑中的神经前体细胞产生神经元,其次是寡细胞和星球细胞.
- 控制从神经生成转变为神经生成的精确机制,特别是寡细胞的产生,仍然不完全理解.
研究的目的:
- 调查Notch信号在调节胚胎发育过程中小基细胞血统细胞的时间和数量的作用.
- 阐明诺奇信号影响寡基生成的分子机制.
主要方法:
- 在小鼠胚胎中利用了ex vivo和子宫内方法.
- 采用了诺奇抑制和过度激活策略.
- 研究了CRISPR/Cas9介导的Hes1和Hes5.5中断的作用.
- 分析了Notch信号,Hes因子和转录因子ASCL1.1之间的相互作用.
主要成果:
- 诺奇抑制降低了寡基细胞系细胞,而诺奇过度激活阻止了寡基生成,维持了原生状态.
- 鉴定出Hes1和Hes5是寡基生成的负调节剂.
- 击败Hes1/Hes5导致ASCL1的表达增加和早期的寡基生.
- 划分过度激活与ASCL1过度表达协同,以促进寡基生成.
结论:
- 痕信号在寡基生育中起着双重作用,促进命运,同时也保持了祖先的地位.
- 在神经元-质切换之前,HES因子介导ASCL1的依赖切割的抑制.
- 一个独立的Notch机制,可能独立于Hes因子,与ASCL1协同作用,促进后期发育中的寡基生.
- 这种精细调节的Notch活动对于及时和适当地产生寡细胞至关重要,确保正确的神经元 - 质开关.
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