The long range goal of this application is to acquire a deeper understanding of the mechanisms that underlie embryonic bone formation. The role and significance of gap junction-mediated cell communication will be evaluated during expression of the osteogenic phenotype in embryonic chick mandibular mesenchyme. These studies are supported by recent findings of a specific association between the presence of two gap junction proteins with bone formation in embryonic facial primordia. These two gap junction proteins, connexin43 and connexin45, are associated principally with two aspects of bone formation. The initiation of osteogenesis is associated with connexin43 and the progressive expression of the differentiating osteogenic phenotype is associated with connexin45. Since these are the only connexins that have been found associated with bone formation, and because of the specificity exhibited by these connexins, this application will focus on the role of connexin expression and of gap junction-mediated cell communication in the establishment of the osteogenic lineage.
Four specific aims are proposed. The first specific aim is to determine whether gap junctional communication is required for expression of the osteogenic phenotype. The second specific aim is to determine whether interference with gap junctional communication will alter the osteogenic phenotype. The third specific aim is to determine whether the expression of mRNA for Cx43 and Cx45 is developmentally regulated. The fourth specific aim is to determine whether the appearance of specific cell adhesion molecules (CAMs) is associated with the expression of either Cx43 or Cx45 in osteogenic mesenchyme. Techniques to be utilized include microsurgery, tissue recombination, cell and organ culture, microinjection, histochemistry, immunocytochemistry, in situ hybridization, and chemical and mechanical cell-loading techniques.
| Minkoff, R; Bales, E S; Kerr, C A et al. (1999) Antisense oligonucleotide blockade of connexin expression during embryonic bone formation: evidence of functional compensation within a multigene family. Dev Genet 24:43-56 |
| Rundus, V R; Marshall, G B; Parker, S B et al. (1998) Association of cell and substrate adhesion molecules with connexin43 during intramembranous bone formation. Histochem J 30:879-96 |
| Minkoff, R; Parker, S B; Rundus, V R et al. (1997) Expression patterns of connexin43 protein during facial development in the chick embryo: associates with outgrowth, attachment, and closure of the midfacial primordia. Anat Rec 248:279-90 |
