Open AccessIRX3/5 regulate mitotic chromatid segregation and limb bud shape
Author(s) -
Hirotaka Tao,
Jean-Philippe Lambert,
Theodora Yung,
Min Zhu,
Noah A. Hahn,
Danyi Li,
Kimberly Lau,
Kendra Sturgeon,
Vijitha Puviindran,
Xiaoyun Zhang,
Wuming Gong,
Xiao Xiao Chen,
Gail I. Anderson,
Daniel J. Garry,
R. Mark Henkelman,
Yu Sun,
Angelo Iulianella,
Yasuhiko Kawakami,
AnneClaude Gingras,
Chi Chung Hui,
Sevan Hopyan
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.180042
Subject(s) - biology , limb bud , primordium , morphogenesis , microbiology and biotechnology , mitosis , chromatid , cell cycle , cohesin , cell division , cell , dna , genetics , chromosome , gene , embryo , chromatin
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 coregulators 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.