Harmonization of L1CAM Expression Facilitates Axon Outgrowth and Guidance of a Motor Neuron

ABSTRACT Brain development requires precise regulation of axon outgrowth, guidance and termination by multiple signaling and adhesion molecules. How the expression of these neurodevelopmental regulators is transcriptionally controlled is poorly understood. The Caenorhabditis elegans SMD motor neurons terminate axon outgrowth upon sexual maturity and partially retract their axons during early adulthood. Here we show that C-Terminal Binding Protein-1 (CTBP-1), a transcriptional corepressor, is required for correct SMD axonal development. Loss of CTBP-1 causes multiple defects in SMD axon development: premature outgrowth, defective guidance, delayed termination and absence of retraction. CTBP-1 controls SMD axon development by repressing the expression of SAX-7 – a L1 cell adhesion molecule (L1CAM). CTBP-1-regulated repression is crucial as deregulated SAX-7/L1CAM causes aberrant SMD axons. We found that axonal defects caused by SAX-7/L1CAM misexpression are dependent on a distinct L1CAM, called LAD-2, which itself plays a parallel role in SMD axon guidance. Our results reveal that harmonization of L1CAM expression controls the development and maturation of a single neuron.