Department of Biochemistry, Faculty of Science, University of Geneva, 30 Quai Ernest Ansermet, Geneva, 1205, Switzerland.
Commun Biol. 2024 Apr 10;7(1):439. doi: 10.1038/s42003-024-06018-7.
The phenomenal diversity of neuronal types in the central nervous system is achieved in part by the asymmetric division of neural precursors. In zebrafish neural precursors, asymmetric dispatch of Sara endosomes (with its Notch signaling cargo) functions as fate determinant which mediates asymmetric division. Here, we found two distinct pools of neural precursors based on Sara endosome inheritance and spindle-microtubule enrichment. Symmetric or asymmetric levels of spindle-microtubules drive differently Sara endosomes inheritance and predict neural precursor lineage. We uncover that CAMSAP2a/CAMSAP3a and KIF16Ba govern microtubule asymmetry and endosome motility, unveiling the heterogeneity of neural precursors. Using a plethora of physical and cell biological assays, we determined the physical parameters and molecular mechanisms behind microtubule asymmetries and biased endosome motility. Evolutionarily, the values of those parameters explain why all sensory organ precursor cells are asymmetric in flies while, in zebrafish spinal cord, two populations of neural precursors (symmetric vs asymmetric) are possible.
中枢神经系统中神经元类型的惊人多样性部分是通过神经前体细胞的不对称分裂实现的。在斑马鱼神经前体细胞中,Sara 内体(及其 Notch 信号货物)的不对称分配作为命运决定因素,介导不对称分裂。在这里,我们根据 Sara 内体的遗传和纺锤体微管的富集发现了两种不同的神经前体细胞池。纺锤体微管的对称或不对称水平驱动 Sara 内体的不同遗传,预测神经前体细胞谱系。我们揭示了 CAMSAP2a/CAMSAP3a 和 KIF16Ba 控制微管的不对称性和内体的运动性,揭示了神经前体细胞的异质性。使用大量的物理和细胞生物学测定,我们确定了微管不对称性和偏向性内体运动的物理参数和分子机制。从进化的角度来看,这些参数的值解释了为什么在果蝇中所有感觉器官前体细胞都是不对称的,而在斑马鱼脊髓中,两种神经前体细胞(对称与不对称)是可能的。