The Expression of TGF-beta1 is Increased in the TGF-beta3 Null Mutant Mice Cleft Palate

During palatal fusion, the medial edge epithelium (MEE) disappears by mean of cell death, epithelial mesenchymal transformation and migration to the oral and nasal palatal epithelia. In the TGF-beta3 null mutant mouse cleft palate, the MEE cells instead survive and differentiate to a stratified keratinised epithelium. This could be due to the abnormal presence of other growth factors in these palates promoting MEE cells survival. Objective: To determine whether the absence of TGF-beta3 produces an unbalanced expression of other growth factors that are usually present during palate development and could account for the survival of MEE cells. Method: We have immunolabeled embryonic day 14.5 C57 TGF-beta3 null mutant and wild type palates with policlonal antibodies directed against the beta1 and beta2 isoforms of the TGF-beta family. Results: Our results show that the expression of TGF-beta1 is greatly increased in the palatal mesenchyme of TGF-beta3 null mutant mice and that the distribution of TGF-beta2 is not altered. In addition, we have found some intensively labelled TGF-beta1 positive cells in the midline epithelial seam of the wild type palates prior to and during its disruption. The increased presence of TGF-beta1 in the mesenchyme of the mutants might be responsible for the decreased cell death observed in their MEE, as it occurs in other systems. Conclusion: Since MEE programmed cell death is one of the most important mechanisms removing MEE cells during palatal fusion, this result points to a direct responsibility for an unbalanced presence of growth factors in the production of the cleft palate occurred in the absence of TGF-beta3.The presence of TGF-beta1 positive cells in the midline epithelial seam of the wild type palates suggests a very active role for TGF-beta1 in the MEE cell fate during palatal fusion. Granted by the Comunidad de Madrid, Ref. 08.6/0042/2000.