Hox cofactors in vertebrate development

Dev Biol. 2006 Mar 15;291(2):193-206. doi: 10.1016/j.ydbio.2005.10.032. Epub 2006 Mar 3.


Hox genes encode homeodomain-containing transcription factors that pattern the body axes of animal embryos. It is well established that the exquisite DNA-binding specificity that allows different Hox proteins to specify distinct structures along the body axis is frequently dependent on interactions with other DNA-binding proteins which act as Hox cofactors. These include the PBC and MEIS classes of TALE (Three Amino acid Loop Extension) homeodomain proteins. The PBC class comprises fly Extradenticle (Exd) and vertebrate Pbx homeoproteins, whereas the MEIS class includes fly Homothorax (Hth) and vertebrate Meis and Prep homeoproteins. Exd was first implicated as a Hox cofactor based on mutant phenotypes in the fly. In vertebrates, PBC and MEIS homeobox proteins play important roles in development and disease. In this review, we describe the evidence that these functions reflect a requirement for Pbx and Meis/Prep proteins as Hox cofactors. However, there is mounting evidence that, like in the fly, Pbx and Meis/Prep proteins function more broadly, and we also discuss how "Hox cofactors" function as partners for other, non-Hox transcription factors during development. Conversely, we review the evidence that Hox proteins have functions that are independent of Pbx and Meis/Prep cofactors and discuss the possibility that other proteins may participate in the DNA-bound Hox complex, contributing to DNA-binding specificity in the absence of, or in addition to, Pbx and Meis/Prep.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Proliferation
  • DNA / metabolism
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins / physiology
  • Embryonic Development*
  • Homeodomain Proteins / physiology*
  • Humans
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / physiology
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins / physiology
  • Transcription Factors / physiology


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • PKNOX1 protein, human
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • Transcription Factors
  • exd protein, Drosophila
  • pbx1 protein, human
  • DNA