Alx-4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions

Dev Dyn. 1998 Oct;213(2):159-69. doi: 10.1002/(SICI)1097-0177(199810)213:2<159::AID-AJA1>3.0.CO;2-F.


We have recently demonstrated that the retinoblastoma family of negative cell cycle regulators can form complexes with a class of developmental factors which contain paired-like (PL) homeodomains (Wiggan et al. [1998] Oncogene 16:227-236). Our screens led to the isolation of a novel PL-homeodomain protein which had been isolated independently by another group and called Alx-4 (Qu et al. [1997] Development 124:3999-4008). Mice homozygous for a targeted null mutation of Alx-4 have several abnormalities, including preaxial polydactyly, suggesting that Alx-4 plays a role in pattern formation in limb buds. In data that we present here, we show that Alx-4 is expressed in mesenchymal condensations of a diverse group of tissues whose development is dependent on epithelial-mesenchymal interactions, many of which are additionally dependent on expression of the HMG-box-containing protein, LEF-1. Alx-4-expressing tissues include osteoblast precursors of most bones, the dermal papilla of hair and whisker follicles, the dental papilla of teeth, and a subset of mesenchymal cells in pubescent mammary glands. We show further that Alx-4 strongly activates transcription from a promoter containing the homeodomain binding site, P2. Optimal activation requires specific sequences in the N-terminal portion of Alx-4 as well as a proline-rich region downstream of the PL-homeodomain, but not the paired-tail at the C terminus. Taken together, our results demonstrate that Alx-4 is a potent transcriptional activator that is expressed at sites of epithelial-mesenchymal interactions during murine embryonic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / embryology
  • Bone and Bones / metabolism
  • COS Cells
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • Embryonic and Fetal Development / genetics
  • Epithelium / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Hair Follicle / embryology
  • Hair Follicle / metabolism
  • Homeodomain Proteins / genetics*
  • In Situ Hybridization
  • Lymphoid Enhancer-Binding Factor 1
  • Mammary Glands, Animal / embryology
  • Mammary Glands, Animal / metabolism
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Promoter Regions, Genetic
  • Tooth / embryology
  • Tooth / metabolism
  • Trans-Activators / genetics*
  • Transcription Factors / genetics
  • Transfection


  • Alx4 protein, mouse
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • DNA