Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development.
Clim-2 (NLI, Lbd1) is one of two related mouse proteins that interact with Lim-domain homeoproteins. In the mouse, embryonic expression of Clim-2 is particularly pronounced in facial ectomesenchyme and limb bud mesenchyme in association with Lim genes, Lhx-6 and Lmx-1 respectively. We show that in common with both these Lim genes, Clim-2 expression is regulated by signals from overlying epithelium. In both the developing face and the limb buds we identify Fgf-8 as the likely candidate signalling molecule that regulates Clim-2 expression. We show that in the mandibular arch, as in the limb, Fgf-8 functions in combination with CD44, a cell surface binding protein, and that blocking CD44 binding results in inhibition of Fgf8-induced expression of Clim-2 and Lhx-6. Regulation of gene expression by Fgf8 in association with CD44 is thus conserved between limb and mandibular arch development.
Tucker
A S
AS
Department of Craniofacial Development, GKT Dental Institute, Kings College, Guy's Hospital, London SE1 9RT, UK.
Al Khamis
A
A
Ferguson
C A
CA
Bach
I
I
Rosenfeld
M G
MG
Sharpe
P T
PT
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D004268:DNA-Binding Proteins; D005314:Embryonic and Fetal Development; D005121:Extremities / Q000254:growth & development*; D051524:Fibroblast Growth Factor 8; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D018960:Hyaluronan Receptors / Q000235:genetics; D006820:Hyaluronic Acid / Q000494:pharmacology; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D008334:Mandible / Q000254:growth & development*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D014157:Transcription Factors / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D006133:Growth Substances; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006820:Hyaluronic Acid