IRX3/5 regulate mitotic chromatid segregation and limb bud shape.

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. © 2020. Published by The Company of Biologists Ltd.

Citation

Hirotaka Tao, Jean-Philippe Lambert, Theodora M Yung, Min Zhu, Noah A Hahn, Danyi Li, Kimberly Lau, Kendra Sturgeon, Vijitha Puviindran, Xiaoyun Zhang, Wuming Gong, Xiao Xiao Chen, Gregory Anderson, Daniel J Garry, R Mark Henkelman, Yu Sun, Angelo Iulianella, Yasuhiko Kawakami, Anne-Claude Gingras, Chi-Chung Hui, Sevan Hopyan. IRX3/5 regulate mitotic chromatid segregation and limb bud shape. Development (Cambridge, England). 2020 Oct 05;147(19)

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PMID: 32907847

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