DEVELOPMENTAL REGULATION OF HIGHLY-ACTIVE ALTERNATIVELY SPLICED FORMSOF AGRIN

Agrin is an extracellular matrix protein involved in clustering acetyl choline receptors during development of the neuromuscular junction. We have previously shown that alternative splicing at three sites genera tes multiple forms of rat agrin and that a novel 8 amino acid insert i s the most important in determining biological activity. In the presen t study we have examined the expression of agrin during development wi th particular emphasis on determining the tissue distribution of the s plicing variants at each site. Our principal observation is that the v ariants containing the sequence most responsible for biological activi ty are expressed exclusively in neural tissue and that their expressio n is highly regulated during development. We also show that muscle exp resses less active forms and that agrin immunoreactivity during synapt ogenesis is initially not limited to synaptic sites, but becomes progr essively restricted to the synapse as development proceeds.