Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.
Development. 2020 Oct 5;147(19):dev180042. doi: 10.1242/dev.180042.
Pattern formation is influenced by transcriptional regulation as well as by morphogenetic mechanisms that shape organ primordia, although factors that link these processes remain under-appreciated. Here we show that, apart from their established transcriptional roles in pattern formation, IRX3/5 help to shape the limb bud primordium by promoting the separation and intercalation of dividing mesodermal cells. Surprisingly, IRX3/5 are required for appropriate cell cycle progression and chromatid segregation during mitosis, possibly in a nontranscriptional manner. IRX3/5 associate with, promote the abundance of, and share overlapping functions with co-regulators of cell division such as the cohesin subunits SMC1, SMC3, NIPBL and CUX1. The findings imply that IRX3/5 coordinate early limb bud morphogenesis with skeletal pattern formation.
形态发生受转录调控以及形态发生机制的影响，这些机制塑造了器官原基，但将这些过程联系起来的因素仍未得到充分认识。在这里，我们表明，IRX3/5 除了在形态发生中具有既定的转录作用外，还通过促进分裂中胚层细胞的分离和插入来帮助塑造肢芽原基。令人惊讶的是，IRX3/5 对于有丝分裂过程中适当的细胞周期进展和染色单体分离是必需的，可能是以非转录方式。IRX3/5 与细胞分裂的共调节因子（如黏合蛋白亚基 SMC1、SMC3、NIPBL 和 CUX1）结合、促进其丰度，并具有重叠的功能。这些发现表明，IRX3/5 协调早期肢芽形态发生与骨骼形态发生。
