哺乳动物的Par3通过Notch信号通路调控发育中大脑新皮质的祖细胞不对称分裂。
Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex.
作者信息
Bultje Ronald S, Castaneda-Castellanos David R, Jan Lily Yeh, Jan Yuh-Nung, Kriegstein Arnold R, Shi Song-Hai
机构信息
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
出版信息
Neuron. 2009 Jul 30;63(2):189-202. doi: 10.1016/j.neuron.2009.07.004.
Asymmetric cell division of radial glial progenitors produces neurons while allowing self-renewal; however, little is known about the mechanism that generates asymmetry in daughter cell fate specification. Here, we found that mammalian partition defective protein 3 (mPar3), a key cell polarity determinant, exhibits dynamic distribution in radial glial progenitors. While it is enriched at the lateral membrane domain in the ventricular endfeet during interphase, mPar3 becomes dispersed and shows asymmetric localization as cell cycle progresses. Either removal or ectopic expression of mPar3 prevents radial glial progenitors from dividing asymmetrically yet generates different outcomes in daughter cell fate specification. Furthermore, the expression level of mPar3 affects Notch signaling, and manipulations of Notch signaling or Numb expression suppress mPar3 regulation of radial glial cell division and daughter cell fate specification. These results reveal a critical molecular pathway underlying asymmetric cell division of radial glial progenitors in the mammalian neocortex.
放射状胶质祖细胞的不对称细胞分裂产生神经元并实现自我更新；然而，对于在子细胞命运特化过程中产生不对称性的机制却知之甚少。在这里，我们发现哺乳动物分隔缺陷蛋白3（mPar3），一种关键的细胞极性决定因子，在放射状胶质祖细胞中呈现动态分布。在间期，它富集于心室端足的侧膜结构域，而随着细胞周期的进展，mPar3会分散并表现出不对称定位。去除或异位表达mPar3均可阻止放射状胶质祖细胞进行不对称分裂，但在子细胞命运特化方面会产生不同的结果。此外，mPar3的表达水平会影响Notch信号通路，对Notch信号通路或Numb表达的操作会抑制mPar3对放射状胶质细胞分裂和子细胞命运特化的调控。这些结果揭示了哺乳动物新皮质中放射状胶质祖细胞不对称细胞分裂背后的关键分子途径。
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