Payumo Alexander Y, Walker Whitney J, McQuade Lindsey E, Yamazoe Sayumi, Chen James K
†Department of Chemical and Systems Biology, ‡Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, United States.
ACS Chem Biol. 2015 Jun 19;10(6):1466-75. doi: 10.1021/cb5010178. Epub 2015 Mar 17.
In addition to their cell-autonomous roles in mesoderm development, the zebrafish T-box transcription factors no tail a (ntla) and spadetail (spt/tbx16) are required for medial floor plate (MFP) formation. Posterior MFP cells are completely absent in zebrafish embryos lacking both Ntla and Spt function, and genetic mosaic analyses have shown that the two T-box genes promote MFP development in a non-cell-autonomous manner. On the basis of these observations, it has been proposed that Ntla/Spt-dependent mesoderm-derived signals are required for the induction of posterior but not anterior MFP cells. To investigate the mechanisms by which Ntla and Spt regulate MFP development, we have used photoactivatable caged morpholinos (cMOs) to silence these T-box genes with spatiotemporal control. We find that posterior MFP formation requires Ntla or Spt activity during early gastrulation, specifically in lateral margin-derived cells that converge toward the midline during epiboly and somitogenesis. Nodal signaling-dependent MFP specification is maintained in the absence of Ntla and Spt function; however, midline cells in ntla;spt morphants exhibit aberrant morphogenetic movements, resulting in their anterior mislocalization. Our findings indicate that Ntla and Spt do not differentially regulate MFP induction along the anterior-posterior axis; rather, the T-box genes act redundantly within margin-derived cells to promote the posterior extension of MFP progenitors.
除了在中胚层发育中发挥细胞自主作用外,斑马鱼的T盒转录因子无尾a(ntla)和尖尾(spt/tbx16)是内侧底板(MFP)形成所必需的。在缺乏Ntla和Spt功能的斑马鱼胚胎中,后部MFP细胞完全缺失,遗传镶嵌分析表明这两个T盒基因以非细胞自主方式促进MFP发育。基于这些观察结果,有人提出,依赖Ntla/Spt的中胚层衍生信号是诱导后部而非前部MFP细胞所必需的。为了研究Ntla和Spt调节MFP发育的机制,我们使用了光激活笼化吗啉代寡核苷酸(cMOs)来时空控制沉默这些T盒基因。我们发现,后部MFP的形成在原肠胚形成早期需要Ntla或Spt活性,特别是在侧缘衍生细胞中,这些细胞在外包和体节形成过程中向中线汇聚。在缺乏Ntla和Spt功能的情况下,依赖于Nodal信号的MFP特化得以维持;然而,ntla;spt突变体中的中线细胞表现出异常的形态发生运动,导致它们向前错位。我们的研究结果表明,Ntla和Spt不会沿前后轴差异调节MFP诱导;相反,T盒基因在边缘衍生细胞中发挥冗余作用,以促进MFP祖细胞的向后延伸。