The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Non-autonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit
2017
During nervous system development, neurons and their progenitors 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. Here we demonstrate that in C.
elegans , nfm-1 is required for the ability of Q cells and their descendants to extend
protrusions and to migrate, but is not required for direction of migration. Using a
combination of mosaic analysis and cell-specific expression, we show that NFM-1 is
required non-autonomously, possibly in muscles, to promote Q lineage migrations. We
also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1 ,
which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might
be involved in the generation of an extracellular cue that promotes Q neuroblast
protrusion and migration that acts with or in parallel to SLT-1. In vertebrates, NF2 and
Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in
regulating migratory events.
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