Legué Emilie, Riedel Elyn, Joyner Alexandra L
Department of Developmental Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Development. 2015 May 1;142(9):1661-71. doi: 10.1242/dev.120287. Epub 2015 Apr 1.
The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.
哺乳动物的小脑由大小和形状各异的褶皱组成，这些褶皱容纳着不同的神经回路。叶片形成的一个关键因素是颗粒细胞（GCs）的产生，颗粒细胞是大脑中数量最多的神经元类型。我们使用克隆分析来揭示小脑形态发生背后的整体以及特定叶片大小的细胞行为。与大多数神经前体细胞不同，GC前体细胞进行对称分裂，这解释了它们的大量增殖。我们发现定向细胞分裂是小脑整体前后极化生长以及GC克隆几何形状的基础。克隆几何形状通过分化中的GCs的中外侧定向迁移和被动扩散进一步细化。最引人注目的是，每个裂隙的底部充当GC前体扩散的边界，我们认为这使得每个叶片能够作为一个发育单元进行调控。事实上，长叶片和短叶片中克隆的几何形状和大小是不同的。此外，在叶片较短的engrailed 1/2突变体中，克隆细胞数量和几何形状与野生型小鼠短叶片中的克隆最为相似。因此，小脑具有模块化的发育模式，允许细胞分裂平面和分裂次数受到不同调控，以确保将适当数量的细胞分配到每个叶片中。
