The invariant cell-cell interactions occurring during C. elegans development offer unique opportunities to discover how growing axons may receive guidance cues from neighboring cells. The
mnm-2 mutant was isolated because of its defects in the axon trajectory of the bilateral M2 pharyngeal neurons in C. elegans. We found that
mnm-2 enhances the effects of many growth cone guidance mutations on these axons, suggesting that it performs a novel function during axon guidance. We cloned
mnm-2 and found that it encodes a protein with three C2H2 zinc finger domains related to the Kruppel-like Factor protein family.
mnm-2 is expressed only transiently in the M2 neuron, but exhibits a sustained expression in its sister cell, the M3 neuron. Strikingly, the expression of
mnm-2 is not sustained in the M3 cell of the
mnm-2 mutant, indicating that this gene positively regulates itself in that cell. Electropharyngeograms also indicate that the M3 cell is functionally impaired in the
mnm-2 mutant. We used an M3-specific promoter to show that the M2 axon defect can be rescued by expression of
mnm-2 in its sister cell M3. The same promoter was used to express the pro-apoptotic gene
egl-1 to kill the M3 cell, which resulted in an M2 axon guidance defect similar to that found in the
mnm-2 mutant. Our results suggest an M2 axon guidance model in which the M3 cell provides an important signal to the growth cone of its sister M2 and that this signal and the proper differentiation of M3 both depend on
mnm-2 expression. This mechanism of axon guidance regulation allows fine-tuning of trajectories between sister cells.