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

Abstract

Inositol phosphates (IPs) play important roles in nervous system development and function. One of these roles uncovered by loss-of-function studies, is that IP isomers are essential for 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 ippk-1 embryos display improper alignment of VNC neuroblasts and delays in rosette-mediated convergent extension (CE). 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 inositol metabolism is important for regulating CE in C. elegans and suggest that IP isomers play a conserved role in the formation of central nerve cords.