PRJNA575061
IRX3 and IRX5 regulate sister chromatid segregation and limb bud shape
Pattern formation is influenced by transcriptional regulation as well as by morphogenet-ic 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 appropri-ate cell cycle progression and sister chromatid segregation, likely in a nontranscriptional manner. IRX3/5 bind with, promote the abundance of, and share overlapping functions with coregulators of cell division such as the cohesin subunits SMC1 and CUX1. The findings im-ply that IRX3/5 coordinate early limb bud morphogenesis with skeletal pattern formation.