The C. elegans M3 neuron guides the growth cone of its sister cell M2 via the Krüppel-like zinc finger protein MNM-2.
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 Krüppel-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.
Rauthan
Manish
M
Department of Chemical and Biological Engineering, Chalmers University, S-405 30, Göteborg, Sweden.
Mörck
Catarina
C
Pilon
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051741:Kruppel-Like Transcription Factors; C524629:MNM-2 protein, C elegans