Nuclear hormone receptor regulation of Caudal mediates ventral nerve cord assembly in C. elegans.

The regulatory network governed by CDX transcription factors in mammals and their ortholog PAL-1 in C. elegans play critical roles in early nervous system development. In nematodes, proper expression of PAL-1 is required for assembly and extension of the ventral nerve cord (VNC). Despite this importance, how PAL-1 is regulated in the nervous system and its precise role remains unclear. We identified an upstream regulatory region within the pal-1 promoter that drives pal-1 expression in a subset of DD and DA neural progenitors during VNC assembly. We have identified a loss of pal-1 in motor neuron progenitors leads to delays in multicellular rosette formation and resolution during VNC formation. We show that a region upstream of the promoter as well as in the nuclear hormone receptor sex-1 result in complete loss of PAL-1 expression in two subtypes of VNC neurons. Restoration of PAL-1 in the VNC through extrachromosomal expression is sufficient to rescue assembly defects in pal-1 and partially rescue defects in sex-1 mutants. Together, our findings suggest that tissue-specific activity facilitates convergence-extension in the C. elegans VNC during its assembly. Given the role of CDX and planar cell polarity proteins during neural tube formation in mammals this work may provide insights and further tools to examine regulatory pathways during nervous system development.