The C. elegans NF2/Merlin Molecule NFM-1 Non-Autonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

Abstract

AbstractDuring nervous system development, neurons and their progenitors often migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to Neurofibromatosis Type II, characterized by benign tumors of glial tissues. These molecules contain Four-point-one Ezrin Radixin Moesin (FERM) domains characteristic of cytoskeletal-membrane linkers, and vertebrate NF2 is required for epidermal integrity. Vertebrate NF2 can also regulate several transcriptional pathways including the Hippo pathway. Here we demonstrate that in C. elegans, nfm-1 is required for complete migration of AQR and PQR, and that it likely acts outside of the Q cells themselves in a non-autonomous fashion. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. In vertebrates, NF2 can control Slit2 mRNA levels through the hippo pathway in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migration.