Regulation of apoptosis during development: input from the extracellular matrix (review)

Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling during development. Extensive investigations have led to the identification of many genes that participate in the regulation of cell death execution. These include the caspases and nucleases, which are involved in the degradation of cellular proteins and nuclear DNA to initiate the irreversible death process. In addition, several families of proteins like Bcl-2 superfamily can either prevent or promote cell death. The function of these proteins are getting to be understood. On the other hand, how these proteins are regulated remains to be investigated. This is in part due to the presence of diverse upstream signals that can influence cell fate. One such signal is the remodeling of the extracellular matrix (ECM), which is largely due to the action of matrix metalloproteinases (MMPs). The regulation of MMPs and ECM remodeling has been shown to affect apoptosis in different systems, including the apoptotic remodeling of the intestine during Xenopus laevis metamorphosis and post-lactation involution of the mouse mammary gland. Current evidence suggests that ECM regulates cell fate at least in part through its membrane receptors, the integrins, which in turn send the signal through yet poorly understood pathways to the nucleus to regulate gene expression.