Novel neurodevelopmental genes in C. elegans

Victoria Cerdeira, Myriam Ares, Lise Rivollet, and Claire Bénard

Dept. Biological Sciences, CERMO-FC Research Center, Université du Québec à Montréal, Canada

Ongoing research with C. elegans continues to uncover fundamental principles of nervous system development and function. Neuron migration, axon guidance and dendritic spine development are essential to establish functional neural circuits. Our goal here is to study cellular and molecular mechanisms that mediate neuronal development, including that of dendritic spines. For this, we are characterizing several genes named mau (maternal-effect uncoordinated), which are defined by mutations isolated in a screen for maternal-effect viable mutations (Hekimi et al., 1995; our unpublished results). mau mutant animals display morphological and behavioural defects that vary in penetrance and expressivity. Our phenotypic analyses of mau mutants reveal that their locomotion is abnormal and variable over time, with episodes of paralysis, spasms and altered body postures. mau mutants have defective axon guidance, including left/right guidance choice at the ventral midline. Moreover, mau mutants display defects in dendritic spines number and distribution, as well as in synaptic transmission. Altered synaptic connectivity and plasticity, including at dendritic spines, are linked to early-onset schizophrenia, which is a very rare disease (prevalence <0,3%); (Moyer et al., 2015).We are progressing towards molecularly identifying and characterizing the mau mutants, which will provide insights on how these novel genes contribute to neuronal development, including of dendritic spines in vivo.

Given the high evolutionary conservation of neuronal development and function between C. elegans and humans, elucidating dendritic spines formation and plasticity is expected to provide key insights for the development of strategies to diagnose and treat rare neurological conditions such as early-onset schizophrenia.