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

Abstract

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 regionspecific 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 regionspecific 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.

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

“…IGF-1 has been associated with variation in dog breed size [82], but a function for IGF-1 signaling in skull formation is less well understood (though see [83, 84]). In the extracellular matrix, Igf proteins bind to Igf binding proteins, and the cellular responses to Igf proteins are strongly dependent on the presence of different Igf binding proteins [54].…”

Systematic analysis of lncRNAs, miRNAs and mRNAs for the identification of biomarkers for osteoporosis in the mandible of ovariectomized mice

“…By contrast, PPARγ agonist has been shown to suppress inflammatory periodontal bone loss by inhibiting osteoclastogenesis (51). The insulin-like growth factor (Igf) family, as well as other growth factor families (Hh, Wnt, Tgf-Bmp, Mapk-Fgf and Notch), which implement biological function via the insulin signaling pathway, may contribute to the merging of the mandibular arch (52). Variations in the promoter region of the IGF-1 gene have been shown to be associated with BMD and the risk of osteoporosis in a Chinese post-menopausal population (53,54).…”

Upper jaw development in the absence of teeth: New insights for craniodental evo‐devo integration

“…One reason is likely the different tissue origins of the upper and lower jaws (Nakatomi et al, ). At least in mammals, another reason for this difference may be structural; the dentary bone derives from a relatively simple‐shaped jaw primordium that fuses in just one location, the MdP midline, by E11 (Fujita, Taya, Shimazu, Aoba, & Soeno, ). There is no need to regulate to the same extent cell proliferation and death to facilitate MdP merging or fusion as there is with the three upper jaw prominences.…”