Grimes Daniel T, Burdine Rebecca D
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Trends Genet. 2017 Sep;33(9):616-628. doi: 10.1016/j.tig.2017.06.004. Epub 2017 Jul 15.
Vertebrates exhibit striking left-right (L-R) asymmetries in the structure and position of the internal organs. Symmetry is broken by motile cilia-generated asymmetric fluid flow, resulting in a signaling cascade - the Nodal-Pitx2 pathway - being robustly established within mesodermal tissue on the left side only. This pathway impinges upon various organ primordia to instruct their side-specific development. Recently, progress has been made in understanding both the breaking of embryonic L-R symmetry and how the Nodal-Pitx2 pathway controls lateralized cell differentiation, migration, and other aspects of cell behavior, as well as tissue-level mechanisms, that drive asymmetries in organ formation. Proper execution of asymmetric organogenesis is critical to health, making furthering our understanding of L-R development an important concern.
脊椎动物的内脏器官在结构和位置上呈现出显著的左右不对称性。运动纤毛产生的不对称流体流动打破了对称性,导致仅在左侧中胚层组织内稳健地建立起一个信号级联反应——即Nodal-Pitx2信号通路。该通路作用于各种器官原基,指导它们进行特定侧的发育。最近,在理解胚胎左右对称性的打破以及Nodal-Pitx2信号通路如何控制侧向细胞分化、迁移和细胞行为的其他方面,以及驱动器官形成不对称性的组织水平机制方面都取得了进展。正确执行不对称器官发生对健康至关重要,这使得加深我们对左右发育的理解成为一个重要关注点。