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 hel...

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Veröffentlicht in:Development (Cambridge) 2020-10, Vol.147 (19)
Hauptverfasser: Tao, Hirotaka, Lambert, Jean-Philippe, Yung, Theodora M, Zhu, Min, Hahn, Noah A, Li, Danyi, Lau, Kimberly, Sturgeon, Kendra, Puviindran, Vijitha, Zhang, Xiaoyun, Gong, Wuming, Chen, Xiao Xiao, Anderson, Gregory, Garry, Daniel J, Henkelman, R Mark, Sun, Yu, Iulianella, Angelo, Kawakami, Yasuhiko, Gingras, Anne-Claude, Hui, Chi-Chung, Hopyan, Sevan
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container_end_page
container_issue 19
container_start_page
container_title Development (Cambridge)
container_volume 147
creator Tao, Hirotaka
Lambert, Jean-Philippe
Yung, Theodora M
Zhu, Min
Hahn, Noah A
Li, Danyi
Lau, Kimberly
Sturgeon, Kendra
Puviindran, Vijitha
Zhang, Xiaoyun
Gong, Wuming
Chen, Xiao Xiao
Anderson, Gregory
Garry, Daniel J
Henkelman, R Mark
Sun, Yu
Iulianella, Angelo
Kawakami, Yasuhiko
Gingras, Anne-Claude
Hui, Chi-Chung
Hopyan, Sevan
description 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.
doi_str_mv 10.1242/dev.180042
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subjects Animals
Blotting, Western
Chromatids - metabolism
Chromosome Segregation - genetics
Chromosome Segregation - physiology
Female
Fluorescent Antibody Technique
HEK293 Cells
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Immunoprecipitation
Limb Buds - embryology
Limb Buds - metabolism
Mass Spectrometry
Mice
Mitosis - genetics
Mitosis - physiology
Pregnancy
Real-Time Polymerase Chain Reaction
RNA-Seq
Transcription Factors - genetics
Transcription Factors - metabolism
title IRX3/5 regulate mitotic chromatid segregation and limb bud shape
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