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. Highlights - ipmk-1 and ippk-1 mutants display neuron position defects in the ventral nerve cord (VNC). - ippk-1 mutants display disorganization in VNC neuronal progenitors during VNC assembly. - IPPK-1 is involved in convergent extension during VNC formation. - Exogenous IP6 rescues larval and embryonic defects in ippk-1 mutants.