IPPK-1 and IP6 contribute to ventral nerve cord assembly in C. elegans

Inositol phosphates (IPs) are essential for the development and function of the nervous system. Loss-of-function studies, which demonstrate the importance of specific IP isomers, show their critical role in proper neural tube formation. In this study, we show that inositol pentakisphosphate 2-kinase (IPPK-1), the kinase that phosphorylates IP5 to generate IP6, is involved in assembling the ventral nerve cord (VNC) in C. elegans. We show that mutations in ippk-1 lead to the mispositioning of motor neurons along the VNC of newly hatched larvae. These positioning defects reflect disruption of VNC assembly during embryogenesis, as VNC neuronal progenitors in ippk-1 embryos display a more compact organization after arising on the left and right sides of the embryo, delays in rosette-mediated convergent extension, and defects in cell intercalation. We further show that injection of exogenous IP6 into the gonads of ippk-1 mutants can rescue both embryonic and neuron positioning defects. Our findings indicate that IP isomers, particularly IP6, are important for ventral nerve cord formation in C. elegans. Along with their role in neural tube formation in vertebrates, these results suggests that IP isomers play an ancient role in central nerve cord development.