An understanding of the mechanisms that underlie primary palate development is necessary for further progress to be made in research related to malformations such as cleft lip and palate. From our past studies we have determined that an orderly, sequential pattern of decline in rates of cell proliferation produces region-specific differences in growth rates throughout the primarly palate of the avian embryo. This pattern of decline was closely associated with the appearance of subpopulations of cells which exit from rapidly proliferating pools and which appeared to be quiescent. Recent studies suggest that quiescent and/or slow cycling cells were ultimately found in chondrogenic regions and that these cells undergo a cell cycle block prior to overt chondrogenesis. Correlative studies of cell communication revealed that the distribution of gap junctions was non-random and that the highest concentrations were found in the subepithelial mesenchyme of the maxillary process. These data, when integrated with our cell cycle data for the same regions, suggest that relationships exist between patterns of cell communication, the pattern of change in cell cycle kinetics, and epithelial-mesenchymal interaction. Future efforts will be directed toward determining (1) the extent to which epithelial-mesenchymal interaction is necessary for the induction or maintenance of patterns of cell communication, (2) whether epithelial-mesenchymal interaction is necessary for the maintenance of cell proliferation rates in subjacent mesenchyme, (3) what sequential, and potentially causal, relationships exist between alterations in epithelial-mesenchymal interaction, changes in the pattern of cell communication and the maintenance of cell proliferation rates, and (4) to determine the effect of uncoupling of cell communication on cell cycle progression. Fluorescence immunocytochemistry, transmission electron microscopy, autoradiography, organ culture, and tissue recombination techniques will be employed. Microinjection of individual cells with antibody to the 27,000 dalton gap junctional protein will be used to block cell communication. The findings from this project will be extended in other studies for analysis of the pathogenesis of malformations in mammalian embryos.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007674-02
Application #
3221379
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Dentistry/Oral Hygn
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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