The formation of extracellular basement membranes is intimately associated with cell differentiation and tissue development in mammalian embryogenesis. Furthermore, alterations of basement membrane structure are associated with human conditions such as neoplastic disease and diabetes. However, little is known about the genetic mechanisms controlling the biogenesis and function of basement membranes. Therefore, the role of the basement membrane in these normal and pathologic processes remains unknown. Examination of the structure and regulation of the murine gene encoding the B2 subunit of the major basement membrane glycoprotein laminin is proposed. Recombinant DNA techniques will be used to prepare molecular clones of the B2 gene and its messenger RNA. Molecular clones of mRNA sequences for the other subunits of laminim will also be sought. Using these molecular tools, the genetic mechanism(s) controlling the rate of synthesis of laminin subunits in F9 embryonal carcinoma cells will be determined. The structure of the B2 gene will be established using nucleic acid hybridization and sequencing techniques, and electron microscopy. The expression of the laminin gene will be measured directly in developing embryos using nucleic acid hybridization techniques.
| Chang, H S; Kim, N B; Phillips, S L (1996) Positive elements in the laminin gamma 1 gene synergize to activate high level transcription during cellular differentiation. Nucleic Acids Res 24:1360-8 |
| Chakravarti, S; Hassell, J R; Phillips, S L (1993) Perlecan gene expression precedes laminin gene expression during differentiation of F9 embryonal carcinoma cells. Dev Dyn 197:107-14 |
