Cell Adhesion Molecules and Palate Fusion in TGF-β3 Null Mice

TGF-β3 null mutant mice from different genetic backgrounds show cleft palate with diverse severity, revealing variation in palatal shelf adhesion. Previous work by this research group demonstrated an altered pattern of expression of Integrin-β1 in the palatal medial edge epithelium (MEE) superficial cells in the C57BL/6J TGF-β3 null embryo compared to the wild type. Objectives: To determine whether: 1.- the changes observed alter palatal shelf adhesion/fusion. 2.- there are any differences in the presence/distribution of Integrin-β1 and other cell adhesion molecules (CAM) in the MEE of TGF-β3 null mice from C57BL/6J (bearing complete cleft palate) and Albino-Swiss (where the middle third of the palate is adhered) strains, that may explain the different MEE adhesion in them. Methods: 1.- Immunolabelling with antibodies against Integrin-β1, Integrin-α5 and ICAM-1 on paraffin sections from embryonic day 14.5 (E14.5) C57 BL/6J and Albino-Swiss wild type and TGF-β3 null mutant mice. 2.- Addition of anti Integrin-β1 or Integrin-α5 blocking antibodies to E13.5 mouse palates and measurement of the resulting MEE adhesion and fusion. Results: Compared to the wild type, changes in the presence/distribution of Integrin-β1, Integrin-α5 and ICAM-1 are observed in the MEE from both strains of mice, although subtle differences in the presence of these molecules are observed between them. Blocking Integrin-α5 function in palate cultures leads to a decrease in palatal shelf adhesion. Conclusion: The presence/distribution of some CAM molecules in the MEE is altered in the cleft palate presented by TGF-β3 null mutant mice of two different strains, and this is likely one of the factors causing this disease. This work has been supported by grants from the Comunidad Autónoma de Madrid (08.6/ 0001.1/2003) and Fondo de Investigación Sanitaria (PI030185).