Lin Juntang, Wang Congrui, Yang Ciqing, Fu Sulei, Redies Christoph
Institute of Anatomy I, University of Jena School of Medicine, Jena University Hospital, D-07743, Jena, Germany.
College of Life Science and Technology, Xinxiang Medical University, 453003, Xinxiang, China.
J Comp Neurol. 2016 Apr 1;524(5):940-62. doi: 10.1002/cne.23885. Epub 2015 Sep 9.
Pax3 and Pax7 are closely related transcription factors that are widely expressed in the developing nervous system and somites. In the CNS, both genes are expressed in the dorsal part of the neural tube during development. Pax3 and Pax7 are involved in the sonic hedgehog (Shh) signaling pathway and are inhibited by Shh overexpression. The present study confirms in vivo that Pax3 overexpression represses the expression of Pax7, whereas Pax7 overexpression endogenously enhances and ectopically induces the expression of Pax3 in the developing chicken spinal cord. Overexpression of Pax3 and Pax7 represses the endogenous expression of cadherin-7, a member of the cadherin family of morphogenetic genes, and induces its ectopic expression. The present study also shows that overexpression of Pax3 and Pax7 changes the fate and morphology of cells in the neuroepithelial layer and induces the expression of postmitotic neuronal markers. We show that both Pax3 and Pax7 promote the differentiation of neural progenitor cells into neurons. Furthermore, the downregulation of Pax3 and Pax7 with specific shRNAs results in apoptosis in the developing spinal cord. Collectively, these results suggest that the transcription factors Pax3 and Pax7 play important roles in regulating morphogenesis and cell differentiation in the developing spinal cord.
Pax3和Pax7是密切相关的转录因子,在发育中的神经系统和体节中广泛表达。在中枢神经系统中,这两个基因在发育过程中均在神经管的背侧表达。Pax3和Pax7参与音猬因子(Shh)信号通路,并受到Shh过表达的抑制。本研究在体内证实,Pax3过表达会抑制Pax7的表达,而Pax7过表达会在内源性增强并异位诱导发育中的鸡脊髓中Pax3的表达。Pax3和Pax7的过表达会抑制形态发生基因钙黏蛋白家族成员钙黏蛋白-7的内源性表达,并诱导其异位表达。本研究还表明,Pax3和Pax7的过表达会改变神经上皮层细胞的命运和形态,并诱导有丝分裂后神经元标志物的表达。我们发现Pax3和Pax7均促进神经祖细胞向神经元的分化。此外,用特异性短发夹RNA下调Pax3和Pax7会导致发育中的脊髓发生凋亡。总体而言,这些结果表明转录因子Pax3和Pax7在调节发育中的脊髓的形态发生和细胞分化中发挥重要作用。