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    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.


    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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