Translating genetic, biochemical and structural information to the calpain view of development.

Embryonic development repeatedly deploys a finite number of signaling pathways to control a multitude of processes such as patterning, growth and differentiation. Diversity in gene expression resulting from these signals depends on the epigenetic landscape as well as the network of interactions between different pathways at a given time. A third mechanism to generate diversity from a sole signal is to modify downstream pathway effectors by modulatory protein activity. The calcium-dependent calpain proteases are modulatory proteases that cleave proteins at specific sites, generating fragments, or neoproteins, with novel functions. Among calpain substrates are effectors of the Wnt and NFκB pathways, ERK pathway and ionic channel receptors, and cell cycle regulators. Loss of calpain function is associated to muscular dystrophy, deterioration of neural connections and embryonic patterning defects. Here we review the basic features of calpains, the principles that guide regulation by calpain activity, and recent literature on how calpain function controls fundamental aspects of animal development.