Exner Cameron R T, Kim Albert Y, Mardjuki Sarah M, Harland Richard M
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Dev Biol. 2017 May 1;425(1):33-43. doi: 10.1016/j.ydbio.2017.03.015. Epub 2017 Mar 18.
The embryonic precursor of the vertebrate central nervous system, the neural plate, is patterned along the anterior-posterior axis and shaped by morphogenetic movements early in development. We previously identified the genes sall1 and sall4, known regulators of pluripotency in other contexts, as transcriptional targets of developmental signaling pathways that regulate neural development. Here, we demonstrate that these two genes are required for induction of posterior neural fates, the cell shape changes that contribute to neural tube closure, and later neurogenesis. Upon sall1 or sall4 knockdown, defects are associated with the failure of the neural plate to differentiate. Consistent with this, sall-deficient neural tissue exhibits an aberrant upregulation of pou5f3 family genes, the Xenopus homologs of the mammalian stem cell maintenance factor Pou5f1 (Oct4). Furthermore, overexpression of pou5f3 genes in Xenopus causes defects in neural patterning, morphogenesis, and differentiation that phenocopy those observed in sall1 and sall4 morphants. In all, this work shows that both sall1 and sall4 act to repress pou5f3 family gene expression in the neural plate, thereby allowing vertebrate neural development to proceed.
脊椎动物中枢神经系统的胚胎前体——神经板，在发育早期沿前后轴形成模式并通过形态发生运动塑造。我们之前鉴定出基因sall1和sall4，它们在其他情况下是多能性的已知调节因子，作为调节神经发育的发育信号通路的转录靶标。在这里，我们证明这两个基因对于诱导后部神经命运、促成神经管闭合的细胞形状变化以及后期神经发生是必需的。在sall1或sall4敲低后，缺陷与神经板无法分化相关。与此一致的是，缺乏sall的神经组织表现出pou5f3家族基因的异常上调，pou5f3家族基因是哺乳动物干细胞维持因子Pou5f1（Oct4）的非洲爪蟾同源物。此外，在非洲爪蟾中过表达pou5f3基因会导致神经模式形成、形态发生和分化缺陷，这些缺陷与在sall1和sall4 morphants中观察到的缺陷相似。总之，这项工作表明sall1和sall4都在神经板中抑制pou5f3家族基因的表达，从而使脊椎动物神经发育得以进行。
