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Hoxa-5 acts in segmented somites to regulate cervical vertebral morphology

Research output: Contribution to journalArticle

  • Jessica W Chen
  • Soombal Zahid
  • Meghan H Shilts
  • Sara J Weaver
  • Rachel M Leskowitz
  • Samima Habbsa
  • Danielle Aronowitz
  • Karimah P Rokins
  • Yvonne Chang
  • Zena Pinnella
  • Lauren Holloway
  • Jennifer H Mansfield

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)226-40
Number of pages15
JournalMechanisms of Development
Volume130
Issue number4-5
DOIs
Publication statusPublished - 2013

Abstract

The vertebrate axial skeleton (vertebral column and ribs) is derived from embryonic structures called somites. Mechanisms of somite formation and patterning are largely conserved along the length of the body axis, but segments acquire different morphologies in part through the action of Hox transcription factors. Although Hox genes' roles in axial skeletal patterning have been extensively characterized, it is still not well understood how they interact with somite patterning pathways to regulate different vertebral morphologies. Here, we investigated the role of Hoxa-5 in after somite segmentation in chick. Hoxa-5 mRNA is expressed in posterior cervical somites, and within them is restricted mainly to a sub-domain of lateral sclerotome. RNAi-based knockdown leads to cartilage defects in lateral vertebral elements (rib homologous structures) whose morphologies vary within and outside of the Hoxa-5 expression domain. Both knockdown and misexpression suggest that Hoxa-5 acts via negative regulation of Sox-9. Further, Hoxa-5 misexpression suggests that spatial and/or temporal restriction of Hoxa-5 expression is necessary for proper vertebral morphology. Finally, the restriction of Hoxa-5 expression to lateral sclerotome, which we hypothesize is important for its patterning function, involves regulation by signaling pathways that pattern somites, Fgf-8 and Shh.

ID: 13158517