Department of Zoology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
Development. 2013 Dec;140(23):4703-8. doi: 10.1242/dev.100339.
The ascidian larval brain and palps (a putative rudimentary placode) are specified by two transcription factor genes, ZicL and FoxC, respectively. FGF9/16/20 induces ZicL expression soon after the bi-potential ancestral cells divide into the brain and palp precursors at the early gastrula stage. FGF9/16/20 begins to be expressed at the 16-cell stage, and induces several target genes, including Otx, before the gastrula stage. Here, we show that ZicL expression in the brain lineage is transcriptionally repressed by Hes-a and two Blimp-1-like zinc finger proteins, BZ1 and BZ2, in the bi-potential ancestral cells. ZicL is precociously expressed in the bi-potential cells in embryos in which these repressors are knocked down. This precocious ZicL expression produces extra brain cells at the expense of palp cells. The expression of BZ1 and BZ2 is turned off by a negative auto-feedback loop. This auto-repression acts as a delay circuit that prevents ZicL from being expressed precociously before the brain and palp fates split, thereby making room within the neural plate for the palps to be specified. Addition of the BZ1/2 delay timer circuit to the gene regulatory network responsible for brain formation might represent a key event in the acquisition of the primitive palps/placodes in an ancestral animal.
海鞘幼虫的脑和腕（一个假定的原始基板）分别由两个转录因子基因 ZicL 和 FoxC 决定。FGF9/16/20 在早期原肠胚阶段，双潜能祖先细胞分裂为脑和腕前体后，立即诱导 ZicL 表达。FGF9/16/20 在 16 细胞期开始表达，并在原肠胚阶段之前诱导几个靶基因，包括 Otx。在这里，我们表明，在双潜能祖先细胞中，Hes-a 和两个 Blimp-1 样锌指蛋白 BZ1 和 BZ2 转录抑制 ZicL 在脑谱系中的表达。在这些抑制剂被敲除的胚胎中，双潜能细胞中 ZicL 过早表达。这种过早的 ZicL 表达以牺牲腕细胞为代价产生额外的脑细胞。BZ1 和 BZ2 的表达被负反馈环关闭。这种自动抑制作为一个延迟电路，防止 ZicL 在脑和腕命运分裂之前过早表达，从而为腕指定在神经板内留出空间。添加 BZ1/2 延迟计时器电路到负责脑形成的基因调控网络可能代表在原始动物中获得原始腕/基板的一个关键事件。
