Barratt Kristen S, Glanville-Jones Hannah C, Arkell Ruth M
Early Mammalian Development Laboratory, Research School of Biology, Evolution, Ecology and Genetics, The Australian National University, Canberra, ACT 0200, Australia.
Genesis. 2014 Jun;52(6):626-35. doi: 10.1002/dvg.22767. Epub 2014 Mar 17.
The first molecular herald of organ asymmetry during murine embryogenesis is found at the periphery of the node in early-somite stage embryos. Asymmetric gene expression and calcium accumulation at the node occurs in response to a left-ward flow of extracellular fluid across the node, generated by motile cilia within the pit of the node and likely sensed by immotile cilia in the periphery of the node. The ciliation of node cells is controlled by a cascade of node-restricted transcription factor activity during mid-late gastrulation. Mutation of the murine Zic2 transcription factor is associated with random cardiac situs and a loss of asymmetric gene expression at the early-somite node and in the lateral plate. Zic2 is not expressed in these regions but is transiently expressed in the mid-late gastrula node at the time of ciliogenesis. The cilia of the node are overtly abnormal in Zic2 mutant embryos being dysmorphic and short relative to wild-type littermates. The expression of the Noto, Rfx3, and Foxj1 transcription factors known to regulate ciliogenesis is greatly depleted in the mid-gastrula node of mutants, as is the expression of the Pkd1l1 gene required for cilia function. Zic2 appears to be a component of the gene regulatory network that drives ciliation of node cells during gastrulation.
在小鼠胚胎发育过程中，器官不对称的首个分子信号出现在早期体节阶段胚胎的节点周边。节点处的不对称基因表达和钙积累是对细胞外液向左流经节点的反应，这种流动由节点凹陷内的运动纤毛产生，可能由节点周边的不动纤毛感知。在原肠胚中晚期，节点细胞的纤毛形成受一系列节点特异性转录因子活性的控制。小鼠Zic2转录因子的突变与心脏位置随机以及早期体节节点和侧板中不对称基因表达的丧失有关。Zic2在这些区域不表达，但在原肠胚中晚期纤毛形成时在节点中短暂表达。在Zic2突变体胚胎中，节点的纤毛明显异常，相对于野生型同窝仔畜，其形态异常且短小。已知调节纤毛形成的Noto、Rfx3和Foxj1转录因子的表达在突变体的原肠胚中期节点中大幅减少，纤毛功能所需的Pkd1l1基因的表达也是如此。Zic2似乎是原肠胚形成过程中驱动节点细胞纤毛形成的基因调控网络的一个组成部分。
