Exploring the Role for IPPK-1 and PAL-1 in the Genetic Landscape of C. elegans Ventral Nerve Cord Assembly

Abstract

Formation of the neural tube, from which the central nervous system develops, depends on convergent extension (CE) movements that constrict and elongate neuroepithelial tissue. Genetic regulators of CE include components of inositol phosphate metabolism, the caudal CDX transcription factor family, and the non-canonical WNT/planar cell polarity (PCP) pathway. To better understand the genetic mechanisms underlying CE, we examined the assembly of the C. elegans ventral nerve cord (VNC), which undergoes CE during its formation. This process involves the coordination of multiple neuron subtypes and is regulated by the PCP pathway. However, the genetic regulation of VNC assembly and the morphogenetic processes involved remain poorly understood. This dissertation explores the roles of two conserved regulators of embryonic nerve cord assembly in C. elegans: the inositol phosphate (IP) pathway and the transcription factor PAL1/CDX. We found that disruption of the central IP kinase IPPK-1 caused defects in initial contacts between left and right VNC motor neurons and delayed the resolution of multicellular rosettes, which are critical for driving anterior-posterior junction extension. These defects impaired CE, leading to persistent cell contacts later inembryogenesis and resulting in the mispositioning of neurons. Additionally, we identified a region approximately 10 kb upstream of the pal-1 start site that is required for its expression in DA and DD neurons. Loss of the nuclear hormone receptor SEX-1 produced a similar phenotype and exacerbated pal-1 defects in compound mutants. Mutation of both ippk-1 or pal-1 and the PCP component vang-1/Van Gogh, similarly increased severity in neuron positioning defects. This work highlights the regulatory network underlying VNC assembly, which involves tissue-specific transcription factor cascades and coordinated cell movements. Moreover, it demonstrates that nematode VNC assembly shares genetic pathways, mechanisms, and defects with neurulation, suggesting that the VNC serves as a valuable model for further investigation.