Study on the expression of matrix-degrading enzymes and programmed cell death during mammalian development

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To elucidate the significance of the PCD and machinery of the morphogenesis of palate and limb, we investigated the occurrence of the PCD and the expression of matrix-degrading enzymes in vivo using mouse fetuses and carried out a series of experiments in vitro. The results obtained are summarized as follows;1. Palatogenesis1) PCD in the midline epithelial seam is not always necessary for the mesenchymal confluence of palate shelves, 'fusion'. 2) MEE cells have an ability to autonomously differentiate into mesenchymal cells without a contact or adhesion of the opposing palatal shelves. 3) When MEE cells have fail to transform into mesenchymal cells, the MEE cells appear to undergo apoptotic cell death. 4) Matrix metalloproteinases seem to be a key molecule for not only the mesenchymal confluence, but also the terminal differentiation of MEE cells.2. Digit separation of limb bud.1) When PCD occurs in the interdigital tissues prior to digit separation, some of endothelial cells are undergo apoptosis in the regressing marginal venous sinus and interdigital microvascular plexus. 2) PCD in the interdigital tissues appears to directly contribute to the vascular remodeling, but not to digit separation. 3) The expression of gelatinize/MMP-2 mRNA is closely associated with the vascular remodeling that appears to be required for the complete separation of individual digits. 4) In hindlimbs of the Hammer-toe(Hm/Hm) mouse fetuses, the insufficient cell death between digits II and III and between digits III and IV might result in the failure not only of the separation of digits but also of regression of the interdigital microvascular plexus.In conclusion, during mammalian development, the formation of complicated structures are achieved by 'Scrap and Build' of preexisting structures resulting from the expression of matrix-degrading enzymes and the occurrence of PCD.