The long range goal of this research program is to identify the developmental mechanisms responsible for the formation, enlargement and union of the facial primordia. The present specific aims represent continuing analysis of the relationship between epithelial-mesenchymal interaction and patterns of cell communication and cell proliferation. Prior studies indicated that the presence of epithelium had a profound effect on the viability and proliferation of subjacent mesenchyme. Microinjection of fluorescent tracers into cells of explants of recombined tissues revealed patterns of gap junctional communication in subjacent mesenchyme. Other studies, employing immunofluorescent localization with antibodies to gap junction proteins (27kDa and 43kDa) demonstrated unique patterns of distribution in specific locations, such as the nasal placode (27kDa), and patterns of distribution associated with cell proliferation (43kDa). In light of these findings, the following will be done.
Specific Aim #1 : Communication-incompetent cell populations will be prepared and employed in organ culture systems to test the hypotheses: a) developmental signals between epithelium and mesenchyme are transmitted by gap junctions b) blockage of gap junctional communication at the epithelial-mesenchymal interface will affect proliferation of the adjacent communication-competent mesenchyme.
Specific Aim #2 : Immunocytochemistry, employing antibodies to the 43kDa gap junction protein, will be used to test the hypotheses a) that the 43kDa protein is present in the facial primordia and is distributed in a region-specific manner b) its distribution is correlated with previously determined rates of cell proliferation in the facial primordia c) the distribution is concordant (or discordant) with the distribution of the 27kDa gap junction protein.
Specific Aim #3 : The hypothesis that expression of the gene for the 27kDa is developmentally regulated will be tested by a) determining whether expression of the gene is region-specific in the nasal placode b) determining whether expression of the gene is temporally regulated during nasal placode formation c) determining whether expression of the gene is associated with a particular morphogenetic event during nasal placode development. Epithelial-mesenchymal separation and recombination, organ culture, microinjection, electroporation, flow cytometry, immunocytochemistry, in situ hybridization, and autoradiography will be utilized.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007674-05
Application #
3221381
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1986-08-01
Project End
1994-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Dentistry
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
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
Helms, J A; Kim, C H; Hu, D et al. (1997) Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid. Dev Biol 187:25-35
Parker, S B; Hertzberg, E L; Minkoff, R (1994) Modulation of gap junction-mediated intercellular communication in embryonic chick mesenchyme during tissue remodeling in vitro. Cell Tissue Res 275:215-24
Minkoff, R; Rundus, V R; Parker, S B et al. (1994) Gap junction proteins exhibit early and specific expression during intramembranous bone formation in the developing chick mandible. Anat Embryol (Berl) 190:231-41
Pinero, G J; Parker, S; Rundus, V et al. (1994) Immunolocalization of connexin 43 in the tooth germ of the neonatal rat. Histochem J 26:765-70
Minkoff, R; Rundus, V R; Parker, S B et al. (1993) Connexin expression in the developing avian cardiovascular system. Circ Res 73:71-8
Minkoff, R (1991) Cell proliferation during formation of the embryonic facial primordia. J Craniofac Genet Dev Biol 11:251-61
Minkoff, R; Parker, S B; Hertzberg, E L (1991) Analysis of distribution patterns of gap junctions during development of embryonic chick facial primordia and brain. Development 111:509-22

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