Womble Mandy, Amin Nirav M, Nascone-Yoder Nanette
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC 27607, USA.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC 27607, USA.
Dev Biol. 2018 Jul 15;439(2):80-91. doi: 10.1016/j.ydbio.2018.04.021. Epub 2018 Apr 27.
Internal organs exhibit left-right asymmetric sizes, shapes and anatomical positions, but how these different lateralities develop is poorly understood. Here we use the experimentally tractable Xenopus model to uncover the morphogenetic events that drive the left-right asymmetrical lobation of the liver. On the right side of the early hepatic diverticulum, endoderm cells become columnar and apically constricted, forming an expanded epithelial surface and, ultimately, an enlarged right liver lobe. In contrast, the cells on the left side become rounder, and rearrange into a compact, stratified architecture that produces a smaller left lobe. Side-specific gain- and loss-of-function studies reveal that asymmetric expression of the left-right determinant Pitx2c elicits distinct epithelial morphogenesis events in the left side of the diverticulum. Surprisingly, the cellular events induced by Pitx2c during liver development are opposite those induced in other digestive organs, suggesting divergent cellular mechanisms underlie the formation of different lateralities.
内脏器官呈现出左右不对称的大小、形状和解剖位置，但这些不同的左右不对称性是如何形成的，目前还知之甚少。在这里，我们使用易于实验操作的非洲爪蟾模型来揭示驱动肝脏左右不对称叶化的形态发生事件。在早期肝憩室的右侧，内胚层细胞变为柱状并顶端收缩，形成扩大的上皮表面，并最终形成增大的右肝叶。相比之下，左侧的细胞变得更圆，并重新排列成紧密的分层结构，从而产生较小的左叶。特定侧别的功能获得和功能丧失研究表明，左右决定因子Pitx2c的不对称表达在憩室左侧引发了不同的上皮形态发生事件。令人惊讶的是，Pitx2c在肝脏发育过程中诱导的细胞事件与在其他消化器官中诱导的事件相反，这表明不同的细胞机制是不同左右不对称性形成的基础。
