During palate fusion, the midline epithelial seam (MES) cell death is a crucial event for its disappearance. At this time point, both TGF-ß1 and TGF-ß3 are expressed in this epithelium. Objectives: The aim of this work has been to determine the relationship between TGF-ß1 and TGF-ß3 with the cell death observed in the MES prior to palate fusion. Methods: We have performed double labelling of embryonic day 14.5 (E14.5) mouse palates with antibodies against TGF-ß1 and TGF-ß3 and TUNEL, E13.5 wild type or tgf-ß3 null palatal shelf cultures, added or blocked TGF-ß1 in these cultures, and in situ hybridization with tgf-ß1 and tgf-ß3 riboprobes. Results: Our results demonstrate that, in the wild type mouse, MES dead cells are TGF-ß1 positive and TGF-ß3 negative. However, both in the presence or absence of TGF-ß1, cell death only occurs if TGF-ß3 is present. The expression of tgf-ß3 is induced both by the exogenous addition of TGF-ß1 or its neutralization. Conclusion: We thus think that TGF-ß3 is the death inductor of MES cells, and that TGF-ß1 modulates its action. This work has been supported by grants from CM (GR/SAL/0539/2004), FIS (PI03/0185) and UCM/CM to the research group 920202.

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