AXONAL GUIDANCE DEFECTS IN A CAENORHABDITIS-ELEGANS MUTANT REVEAL CELL-EXTRINSIC DETERMINANTS OF NEURONAL MORPHOLOGY

Mutations in the gene unc-53 of Caenorhabditis elegans result in behav ioral and anatomical abnormalities. Immunocytochemistry and electron m icroscopy revealed neuroanatomical defects in all main longitudinal ne rvous tracts. Whole tracts were found to be misguided in specific ways suggesting that unc-53 affects pioneering axons. The four lateral mic rotubule cells (LMs), which are probably pioneering neurons, were exam ined in greatest detail. In the mutants, the processes of the LMs leav e their normal position on the body wall and terminate prematurely. Ex amination of five unc-53 alleles for penetrance and expressivity of th ese defects revealed a spatial restriction in the requirement for unc- 53. The morphology and positioning of the branch of the posterior late ral microtubule cells (PLMs) were also examined. In wild-type animals, the PLM branches lack the ultrastructural specializations of the main process, which include large microtubules, apposition to the cuticle, and a polarized extracellular matrix (the mantle). Two differences we re noted in unc-53 mutants. First, a majority of PLMs branch at random and display an abnormally enlarged branching point and branch cross s ection. The unusual branch morphologies correlate with branch position , rather than PLM length. Second, the ectopic branches display the spe cific ultrastructural features characteristic of the main process. Fur thermore, after entering the ventral nerve cord, the abnormal branches constantly change position relative to the other processes and the hy podermis, retaining their specialized microtubules throughout, but dis playing a mantle only when in direct contact with hypodermis. Taken to gether, these observations suggest that the differentiated features of the PLMs, including process length, branch position, intracellular br anch morphology, and surrounding extracellular matrix, are locally spe cified by cell-extrinsic cues, some of which require unc-53.