Journal
DEVELOPMENT
Volume 147, Issue 19, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.180042
Keywords
Iroquois; Cohesin; Limb development; Mesodermal; cell intercalations; Mitotic chromatid segregation; Morphogenesis
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Funding
- Canadian Institutes of Health Research [137092]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR064195]
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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.
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