Notch signaling plays a well-described role in regulating the formation of neurons from proliferative neural precursors in vertebrates but whether, as in flies, it also specifies sibling cells for different neuronal fates is not known. Ventral spinal cord precursors called pMN cells produce mostly motoneurons and oligodendrocytes, but recent lineage-marking experiments reveal that they also make astrocytes, ependymal cells and interneurons. Our own clonal analysis of pMN cells in zebrafish showed that some produce a primary motoneuron and KA' interneuron at their final division. We investigated the possibility that Notch signaling regulates a motoneuron-interneuron fate decision using a combination of mutant, transgenic and pharmacological manipulations of Notch activity. We show that continuous absence of Notch activity produces excess primary motoneurons and a deficit of KA' interneurons, whereas transient inactivation preceding neurogenesis results in an excess of both cell types. By contrast, activation of Notch signaling at the neural plate stage produces excess KA' interneurons and a deficit of primary motoneurons. Furthermore, individual pMN cells produce similar kinds of neurons at their final division in mib mutant embryos, which lack Notch signaling. These data provide evidence that, among some postmitotic daughters of pMN cells, Notch promotes KA' interneuron identity and inhibits primary motoneuron fate, raising the possibility that Notch signaling diversifies vertebrate neuron type by mediating similar binary fate decisions.

译文

Notch信号在调节脊椎动物增殖性神经前体神经元的形成中起着众所周知的作用,但与蝇类一样,它是否也为不同神经元命运指定同胞是未知的。腹侧脊髓前体称为pMN细胞,主要产生运动神经元和少突胶质细胞,但最近的谱系标记实验表明,它们还制造星形胶质细胞,室间隔膜细胞和中间神经元。我们对斑马鱼中pMN细胞的克隆分析表明,有些在最终分裂时会产生原代运动神经元和KA'中间神经元。我们调查了Notch信号调节Notch活性的突变,转基因和药理操作相结合的可能性,调节运动神经元-interneuronron命运的决定。我们显示持续缺刻活动的缺席产生多余的原运动神经元和KA'interneurons的不足,而神经发生之前的瞬时失活导致两种细胞类型的过量。相比之下,在神经板期激活Notch信号会产生过量的KA'中间神经元和初级运动神经元缺陷。此外,单个pMN细胞在mib突变体胚胎的最终分裂中会产生类似种类的神经元,而这些神经元缺少Notch信号传导。这些数据提供了证据,在pMN细胞的某些有丝分裂后代的女儿中,Notch促进KA'中间神经元身份并抑制原运动神经元命运,从而提高了Notch信号通过介导相似的二元命运决定而使脊椎动物神经元类型多样化的可能性。

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