Alx-4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions.
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.
Hudson
R
R
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
Taniguchi-Sidle
A
A
Boras
K
K
Wiggan
O
O
Hamel
P A
PA
D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D019556:COS Cells; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018859:Hair Follicle / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D051821:Lymphoid Enhancer-Binding Factor 1; D008321:Mammary Glands, Animal / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014070:Tooth / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
C109218:Alx4 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA