Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function

Lizhen Chen, Peng Zhao, Lance Wells, Chris T. Amemiya, Brian G. Condie, Nancy R. Manley

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Hox genes play evolutionarily conserved roles in specifying axial position during embryogenesis. A prevailing paradigm is that changes in Hox gene expression drive evolution of metazoan body plans. Conservation of Hox function across species, and among paralogous Hox genes within a species, supports a model of functional equivalence. In this report, we demonstrate that zebrafish hoxa3a (zfhoxa3a) expressed from the mouse Hoxa3 locus can substitute for mouse Hoxa3 in some tissues, but has distinct or null phenotypes in others. We further show, by using an allele encoding a chimeric protein, that this difference maps primarily to the zfhoxa3a C-terminal domain. Our data imply that the mouse and zebrafish proteins have diverged considerably since their last common ancestor, and that the major difference between them resides in the C-terminal domain. Our data further show that Hox protein function can evolve independently in different cell types or for specific functions. The inability of zfhoxa3a to perform all of the normal roles of mouse Hoxa3 illustrates that Hox orthologues are not always functionally interchangeable.

Original languageEnglish (US)
Pages (from-to)10555-10560
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Jun 8 2010
Externally publishedYes


  • Evolution
  • Hox
  • Parathyroid
  • Thymus
  • Vertebrate

ASJC Scopus subject areas

  • General


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