Hox proteins drive cell segregation and non-autonomous apical remodelling during hindbrain segmentation

Fabrice Prin, Patricia Serpente, Nobue Itasaki, Alex P Gould

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)
264 Downloads (Pure)

Abstract

Hox genes encode a conserved family of homeodomain transcription factors regulating development along the major body axis. During embryogenesis, Hox proteins are expressed in segment-specific patterns and control numerous different segment-specific cell fates. It has been unclear, however, whether Hox proteins drive the epithelial cell segregation mechanism that is thought to initiate the segmentation process. Here, we investigate the role of vertebrate Hox proteins during the partitioning of the developing hindbrain into lineage-restricted units called rhombomeres. Loss-of-function mutants and ectopic expression assays reveal that Hoxb4 and its paralogue Hoxd4 are necessary and sufficient for cell segregation, and for the most caudal rhombomere boundary (r6/r7). Hox4 proteins regulate Eph/ephrins and other cell-surface proteins, and can function in a non-cell-autonomous manner to induce apical cell enlargement on both sides of their expression border. Similarly, other Hox proteins expressed at more rostral rhombomere interfaces can also regulate Eph/ephrins, induce apical remodelling and drive cell segregation in ectopic expression assays. However, Krox20, a key segmentation factor expressed in odd rhombomeres (r3 and r5), can largely override Hox proteins at the level of regulation of a cell surface target, Epha4. This study suggests that most, if not all, Hox proteins share a common potential to induce cell segregation but in some contexts this is masked or modulated by other transcription factors.
Original languageEnglish
Pages (from-to)1492-1502
Number of pages11
JournalDevelopment (Cambridge)
Volume141
Issue number7
Early online date26 Feb 2014
DOIs
Publication statusPublished - 1 Apr 2014

Keywords

  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Cell Movement
  • Chick Embryo
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins
  • Membrane Proteins
  • Mice
  • Rhombencephalon
  • Transcription Factors

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