Molecular signaling at the fusion stage of the mouse mandibular arch: involvement of insulin-like growth factor family.

Fusion of the branchial arch derivatives is a crucial event in the development of the craniofacial architecture. Here, we surveyed the gene expression profile, focusing on the fusion process of the mouse mandibular arch at embryonic day 10.5. In order to identify the genes that are relevant to the midline fusion process, we subdivided the mandibular arch medially and laterally, and determined gene expression using microarray and real-time quantitative PCR. By comparing the transcriptomes of the medial and lateral regions, 362 genes were identified as medial region-specific genes, while 346 genes were designated lateral region-specific. Taken with Gene Ontology analysis, KEGG pathways and Ingenuity Pathway Analysis (IPA), a survey of the medial region-specific gene dataset revealed significant expression of the insulin-like growth factor (Igf) family as well as other growth factor families (Hh, Wnt, Tgf-Bmp, Mapk-Fgf and Notch). To determine the discrete expression pattern of Igf family genes in the medial region, we microdissected the medial part of the mandibular arch into epithelial and mesenchymal components, and found that Igf1 was highly expressed in the mesenchyme, Igf2 and Igf1r were expressed in both the midline epithelium and surrounding mesenchyme, and Igfbp5 was highly expressed in the epithelium. Immunohistochemical findings validated the regional Igf gene expression profiles. Our observations suggest that in the “merging” fusion of the mandibular arch, the Igf cascade may contribute to generation of proliferation pressure from the mesenchyme and preservation of epithelial phenotypes and architecture during mesenchymal confluence.