Borodovsky Nataliya, Ponomaryov Tatyana, Frenkel Shani, Levkowitz Gil
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Dev Dyn. 2009 Apr;238(4):826-34. doi: 10.1002/dvdy.21894.
Neural factors are expressed in neural progenitors and regulate neurogenesis and gliogenesis. Recent studies suggested that these factors are also involved in determining specific neuronal fates by regulating the expression of their target genes, thereby creating transcriptional codes for neuronal subtype specification. In the present study, we show that in the zebrafish the neural gene Olig2 and the transcriptional regulator Sim1 are co-expressed in a subset of diencephalic progenitors destined towards the dopaminergic (DA) neuronal fate. While sim1 mRNA is also detected in mature DA neurons, the expression of olig2 is extinguished prior to terminal DA differentiation. Loss of function of either Olig2 or Sim1 leads to impaired DA development. Finally, Olig2 regulates the expression of Sim1 and gain of function of Sim1 rescues the deficits in DA differentiation caused by targeted knockdown of Olig2. Our findings demonstrate for the first time that commitment of basal diencephalic DA neurons is regulated by the combined action of the neural protein Olig2 and its downstream neuronal specific effector Sim1.
神经因子在神经祖细胞中表达，并调节神经发生和胶质细胞生成。最近的研究表明，这些因子还通过调节其靶基因的表达参与决定特定的神经元命运，从而为神经元亚型特化创建转录密码。在本研究中，我们发现在斑马鱼中，神经基因Olig2和转录调节因子Sim1在注定要成为多巴胺能（DA）神经元命运的间脑祖细胞亚群中共同表达。虽然在成熟的DA神经元中也检测到sim1 mRNA，但在DA终末分化之前olig2的表达就消失了。Olig2或Sim1功能丧失都会导致DA发育受损。最后，Olig2调节Sim1的表达，Sim1功能增强可挽救因靶向敲低Olig2而导致的DA分化缺陷。我们的研究首次证明，基底间脑DA神经元的特化受神经蛋白Olig2及其下游神经元特异性效应因子Sim1的联合作用调控。
