Altered nerve terminal arborization and synaptic transmission in Drosophila mutants of cell adhesion molecule...

This work investigates the role of cell adhesion molecules in development of synaptic connections and functions through a genetic approach. Fasciclin I (Fas I) is an insect glycoprotein capable of mediating homophilic cell adhesion. It has been shown that Fas I is expressed in motor nerve axons and terminals that innervate larval body-wall muscles in Drosophila. Immunohistochemical analysis of these motor nerve terminals has revealed that nerve terminal arborization, quantified by the numbers of the nerve terminal branches and varicosities, is enhanced in the null mutant fas ITE. In contrast, the number of branches and varicosities are reduced in larvae that overexpress the Fas I molecule resulting from additional copies of the fas I transgene in P(fas I+) or the chromosome duplication in Dp(fas I) mutants. Although arborization is altered, the overall stereotypical pattern of nerve terminal innervation of the body-wall muscle fibers is preserved in all the Fas I mutants examined. The voltage-clamp analysis of excitatory junctional currents (ejcs) at the neuromuscular junction indicates that the amplitude of ejcs is reduced in fas ITE, but increased in P(fas I+) and Dp(fas I) compared to that in wild-type larvae. Further electrophysiological analysis shows that the quantal content and the evoked frequency-dependent response are affected in these mutants, indicating a defective presynaptic function in addition to the anatomic abnormality. Therefore, the cell adhesion molecule Fas I may not be essential for target recognition and synaptogenesis at the larval neuromuscular junction, but may play a role in fine-turning nerve terminal arborization and possibly in modifying, directly or indirectly, development of presynaptic functions.