Notch-dependent left-right asymmetry in β-catenin-TCF activity instructs anteroposterior positioning of motor neurons in the C. elegans ventral nerve cord

Abstract

The precise organization of motor neurons along the neuroaxis is essential for nervous system connectivity and function. In newly hatched C. elegans, the ventral nerve cord (VNC) contains 22 motor neurons of three classes, DD, DA, and DB, whose cell bodies are arranged in a stereotyped pattern along the anteroposterior (AP) axis. However, the mechanisms that control motor neuron positioning during nerve cord assembly are not fully understood. Here, we uncover a left-right asymmetry in {beta}-catenin-TCF transcriptional activity that regulates AP motor neuron positioning. Loss of bar-1/{beta}-catenin or pop-1/TCF causes a shift of motor neuron cell bodies toward the anterior, while loss of pry-1/Axin shifts them toward the posterior. We further find that POP-1/TCF activity is asymmetric between the left and right sides of the VNC in a BAR-1-dependent manner. Increasing BAR-1 levels on both sides of the VNC causes a posterior shift in motor neuron cell body placement. During VNC assembly, asymmetric Notch signaling promotes PRY-1 expression in left-side neurons, thereby restricting BAR-1 accumulation to right-side motor neurons, presumably through degradation by the destruction complex. Together, our findings reveal a previously unrecognized pathway in which an initial Notch-dependent left-right asymmetry establishes asymmetric {beta}-catenin-TCF activity to regulate the AP positioning of motor neuron cell bodies along the VNC.