University of Lyon, University of Lyon1, CGΦMC, UMR CNRS 5534, F-69100 Villeurbanne, France.
CNRS UMR 7592, Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Nat Commun. 2015 Feb 27;6:6366. doi: 10.1038/ncomms7366.
The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis. Here we analysed neuroepithelial progenitors in the developing mouse spinal cord to determine whether extracellular signals orient the mitotic spindle. We report that Semaphorin3B (Sema3B) released from the floor plate and the nascent choroid plexus in the cerebrospinal fluid (CSF) controls progenitor division orientation. Delivery of exogenous Sema3B to neural progenitors after neural tube opening in living embryos promotes planar orientation of their division. Preventing progenitor access to cues present in the CSF by genetically engineered canal obstruction affects the proportion of planar and oblique divisions. Sema3B knockout phenocopies the loss of progenitor access to the CSF. Sema3B binds to the apical surface of mitotic progenitors and exerts its effect via Neuropilin receptors, GSK3 activation and subsequent inhibition of the microtubule stabilizer CRMP2. Thus, extrinsic control mediated by the Semaphorin signalling orients progenitor divisions in neurogenic zones.
细胞分裂的空间定向对于组织架构和动态平衡至关重要。在这里,我们分析了发育中的小鼠脊髓中的神经上皮祖细胞,以确定细胞外信号是否会定向有丝分裂纺锤体。我们报告称,脑脊液(CSF)中基板和新形成的脉络丛释放的 Sema3B(Semaphorin3B)控制祖细胞的分裂方向。在活体胚胎神经管开放后将外源性 Sema3B 递送至神经祖细胞,可促进其分裂的平面定向。通过基因工程管腔阻塞阻止祖细胞接触 CSF 中的信号,会影响平面和倾斜分裂的比例。Sema3B 基因敲除可模拟祖细胞无法接触 CSF 的情况。Sema3B 与有丝分裂祖细胞的顶端表面结合,并通过神经纤毛蛋白受体、GSK3 激活以及随后抑制微管稳定剂 CRMP2 发挥作用。因此,Semaphorin 信号介导的外在控制可定向神经发生区的祖细胞分裂。