Genetic analysis ofsynapsk formation in mick

Prc and post.synaptic cells exchange morphogencticaliy importât!t information as synapses form, mature, and rearrange. This bidirectional communication has been best studied at the vertebrate neuroinuscuiai junction, owing to the accessibility and simplicity of this model synapse. Studies of cultuied nerve and muscle have led to Ihe identification of several molecule, capable of acting as synaptic organizers as well as components of then signai tran.sduction pathways. It has been difficult, however, to learn which, il .my, of these molecules are crucial for synaptic development in viva. We have now analy/ed neuromuscular development in "knockout ' mice deficient m se\eral such molecules. Some potential organizing molecules, such as tenasun-C and N-CAM, turn oui to be inessential for formation or régéné rai ion ol neuromuscular junctions. In contrast, (wo components oi the basal lamina >H the synaptic cleft, are essential: mutation of genes encoding either lammm [}2 or agrin leads to severe defects in neuromuscular s\ naptogenesis. Likcv, ise. mutation of intramuscular components thought to be involved in poslsynapiic differentiation leads to devastating developmental defect in some cases ie.g., rapsyn). bul surprisingly mild phenotypes in others (e.g.. utrophm or dystrobrevin). Together, these results begin to define molecules crucial loi synapse formation, and provide insights into the mechanisms by which they act (Supported by NIH.).