title: Differential expression of insulin-like growth factors I and II (IGF I and II), mRNA, peptide and binding protein 1 during mouse palate development: comparison with TGF beta peptide distribution.
abstract: Development of the mammalian secondary palate involves a series of epithelial mesenchymal interactions: during one of these, a mesenchymal signal specifies regionally distinct palatal epithelial differentiation. Extracellular matrix molecules and soluble growth factors may be involved in this signalling process. In this study, we have mapped the expression of the genes for insulin-like growth factors (IGF I and II), the peptides they encode, and the IGF binding protein 1 (IGF BP-1) during murine palatogenesis (embryonic days (E) 12-15). IGF-I gene expression was below detectable levels in the craniofacial region at all ages. IGF-I peptide was at the threshold of immunocytochemical detection and widely distributed in the palatal mesenchyme, decreasing in staining intensity from E12 to E14. By contrast, IGF-II mRNA was intensely localised in several tissues. IGF-II gene expression within the forming palate was developmentally regulated. In the vertical palatal shelves (E12 to E13) IGF-II gene expression was absent. On early E14, in the horizontal prefusion palate, significant expression was present in the palatal mesenchyme, but not the epithelium. Once palatal fusion had occurred, mesenchymal expression fell rapidly to undetectable levels. IGF-II mRNA was next detectable in the secondary palate on late E15 at sites of membranous bone formation. By contrast to the mRNA distribution, IGF-II peptide was localised predominantly in the palatal epithelia (particularly the nasal and medial edge epithelia) but also in the mesenchyme of the E14 prefusion palate. Significantly, the IGF binding protein had a similar distribution pattern to the IGF-II peptide. At all ages, the developing tongue myotubes labelled heavily for IGF-II mRNA, protein and binding protein. These data suggest that IGF-II may play a localised paracrine role during murine palatogenesis, perhaps in the mesenchymal signalling of epithelial differentiation. IGF-II may also serve to coordinate the development of the tongue and palate. The distribution of IGF-II peptide was very similar to that of TGF-beta, suggesting a possible interactive role of these growth factors during palate development. Finally, evidence that the IGF-II gene is imprinted (Ferguson-Smith et al. 1991) and may be the target for uniparental disomy in the human Beckwith Wiedemann syndrome (Henry et al. 1991), which is characterised by the overgrowth of tissues (especially the tongue) expressing IGF II in the embryo, indicates the necessity of reanalysing human cleft palate families for disruption (including uniparental disomy) of the genes encoding IGFs, their receptors and binding proteins.
authors.affiliation: Department of Cell and Structural Biology, University of Manchester, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Ferguson
authors.forename: P M
authors.initials: PM
authors.lastname: Sharpe
authors.forename: B L
authors.initials: BL
authors.lastname: Thomas
authors.forename: F
authors.initials: F
authors.lastname: Beck
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics*; D004848:Epithelium / Q000196:embryology; D015870:Gene Expression / Q000502:physiology*; D005796:Genes / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D017403:In Situ Hybridization; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D010159:Palate / Q000196:embryology*; D013002:Somatomedins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D006133:Growth Substances; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II