Dlx2 over-expression regulates cell adhesion and mesenchymal condensation in ectomesenchyme.
The Dlx family of homeodomain transcription factors have diverse roles in development including craniofacial morphogenesis and consists of 6 members with overlapping expression patterns. Dlx2 is expressed within the developing branchial arches in both the epithelium and mesenchyme and targeted deletion in mice has revealed roles in patterning and development of the craniofacial skeleton. Defects in Dlx2 null mice include skeletal anomalies of proximal branchial arch 1 derivatives while distal elements are largely spared indicating redundancy within the Dlx family. We have investigated the function of Dlx2 using in ovo electroporation and cell culture. Ectopic expression of Dlx2 within the neural tube beginning prior to emigration of neural crest cells at E1.25 drastically inhibits the migration of transfected cells and induces aggregation of transfected neuroepithelial cells within the neural tube at 24 h post-electroporation. By 48 h post-electroporation, the majority of transfected cells formed multicellular aggregates that were found adjacent to the basal side of the neural tube and very few Dlx2 expressing cells migrated to the level of the branchial arches. Similar results were obtained for Dlx5, suggesting these effects may be common to Dlx genes. Electroporation of the Dlx2 expression construct into branchial arch mesenchyme induced N-cadherin and NCAM, a dramatic increase in cell-cell adhesion relative to controls, and resulted in an increase in mesenchymal condensation. These results suggest a role for Dlx genes in regulating ectomesenchymal cell adhesion and supports the possibility that the skeletal dysmorphology seen in Dlx null mice may derive from abnormalities at the condensation stage.
McKeown
Sonja J
SJ
Craniofacial Sciences Consortium, Murdoch Childrens Research Institute, Royal Children's Hospital and University of Melbourne, Parkville 3052, Victoria, Australia.
Newgreen
Donald F
DF
Farlie
Peter G
PG
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D018274:Electroporation; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D004628:Embryonic Structures / Q000166:cytology / Q000502:physiology; D005147:Facial Bones / Q000033:anatomy & histology / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D011784:Quail; D012886:Skull / Q000033:anatomy & histology / Q000196:embryology; D014157:Transcription Factors
D015820:Cadherins; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D019006:Neural Cell Adhesion Molecules; D014157:Transcription Factors