IRX3/5 regulate mitotic chromatid segregation and limb bud shape

Development. 2020 Oct 5;147(19):dev180042. doi: 10.1242/dev.180042.


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.

Keywords: Cohesin; Iroquois; Limb development; Mesodermal cell intercalations; Mitotic chromatid segregation; Morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA-Seq
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Homeodomain Proteins
  • Irx3 protein, mouse
  • Irx5 protein, mouse
  • Transcription Factors