Developmental maxillofacial morphogenesis and relevant molecular regulatory mechanisms in mice

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The present study aimed at elucidating the molecular regulation of mandibular process-fusion and palatogenesis in mouse development. ICR mouse embryos were used. Specimens for gene expression and histomorphology were obtained from the medial region of the pharyngeal and mandibular arches at E9.5-11.5 and palatal processes at E13.5-14.5. Multifaceted events and phenotypic features of mouse craniofacial morphogenesis were investigated histologically and immunohistochemically. Gene expression profiles were analyzed in combination of microarray and real-time PCR. We also explored site-discrete gene expression profiles by comparing the median and lateral portions of the mandibular processes. Mesenchymal cell populations in the specified medial region were collected from cryosections using laser capture microdissection. cDNA microarray analysis disclosed distinct spatial-temporal expression patterns of transcription factors (e.g., Pax, Runx, Snaih, a bundle of growth factors and receptors (e … More .g., Shh, FGFs, TGF β, BMR ET1,), Rho families, and cell adhesion molecules (N-cadherin, CD44). Of interest, a large number of the genes (i.e., Ptx1, Dlx, dHand, eHand, Msx1, Bapx1, Barx1, Fgf2, Fgf8, ET1), which are supposed to be involved in epithelio-mesenchymal interaction, were identified as candidates that were differentially expressed at the medial region of mandibular arches during the fusion process. Genes relevant to skeletal muscle differentiation were also validated to be up- or down-regulated in accordance with the completion to medial fusion of mandibular processes and subsequent tongue development. In parallel studies, we developed organ culture models to assimilate in vivo events of molecular and cellular dynamics involved in mandibular fusion and tongue morphogenesis. In the funded period, we verified the effects of SHH and FGF signals on mandibular process fusions and myogenic cell proliferation, apoptosis and differentiation. The results including 3D constructs of developing mouse craniofacial structures in motion are presented in Web site (http://www.ndu.ac.jp/~pathhome/) as well as in forms of publications and abstracts. Less