The MIG-15 NIK kinase acts cell-autonomously in neuroblast polarization and migration in C. elegans

Abstract

Cell migration is a fundamental process in animal development, including development of the nervous system. In C. elegans, the bilateral QR and QL neuroblasts undergo initial anterior and posterior polarizations and migrations before they divide to produce neurons. A subsequent Wnt signal from the posterior instructs QL descendants to continue their posterior migration. Nck-interacting kinases (NIK kinases) have been implicated in cell and nuclear migration as well as lamellipodia formation. Studies here show that the C. elegans MIG-15 NIK kinase controls multiple aspects of initial Q cell polarization, including the ability of the cells to polarize, to maintain polarity, and to migrate. These data suggest that MIG-15 acts independently of the Wnt signal that controls QL descendant posterior migration. Furthermore, MIG-15 affects the later migrations of neurons generated from Q cell division. Finally, a mosaic analysis indicates that MIG-15 acts cell autonomously in Q descendant migration.

Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration

“…Several transmembrane proteins, DPY-19, MIG-21, UNC-40/DCC (Deleted in Colorectal Cancer), and NF-κB-inducing kinase (NIK) MIG-15, regulate the initial Q-neuroblast polarization, and mutations of these genes reduced Q-neuroblast polarization (8)(9)(10)(11). The C. elegans Wnt/β-catenin pathway activates the expression of the Antennapedia-like Homeobox(Hox) gene mab-5, which is necessary and sufficient to ensure the posterior migration of QL.a (the anterior descendant of QL) and QL.ap (the posterior descendant of QL.a) (12)(13)(14)(15)(16)(17).…”

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration

“…Scoring was done using Pgcy-32, which is expressed exclusively in AQR, PQR, and URXl/r (Chapman et al 2008). The position of AQR and PQR was scored as previously described using a compound fluorescent microscope (Chapman et al 2008;Dyer et al 2010).…”

“…Neuron migration is an important aspect of nervous system development and many neurons and neuroblasts migrate from their initial birthplace to specific regions of the periphery (neural crest) or cortex. The Q neuroblasts of Caenorhabditis elegans represent a tractable and well-studied model for Hox genecontrolled neuroblast migration (Chapman et al 2008;Middelkoop and Korswagen 2014). The Q neuroblasts Q right (QR) and Q left (QL) are bilaterally symmetric cells that undergo identical patterns of division, migration, and apoptosis to produce three neurons each (Sulston and Horvitz 1977).…”

“…The Q neuroblasts Q right (QR) and Q left (QL) are bilaterally symmetric cells that undergo identical patterns of division, migration, and apoptosis to produce three neurons each (Sulston and Horvitz 1977). QR on the right side of the animal migrates anteriorly, undergoing cell division and migration, giving rise to three neurons, with AQR migrating the farthest residing near the posterior pharyngeal bulb (Sulston and Horvitz 1977;Chapman et al 2008). QL migrates posteriorly undergoing identical cell divisions, giving rise to three neurons, of which PQR migrates the farthest to reside posterior to the anus, near the phasmid ganglion (Chalfie et al 1983;Kenyon 1986;Salser and Kenyon 1992;Whangbo and Kenyon 1999;Korswagen et al 2000;Chapman et al 2008).…”

“…The mab-5(e1751) gain-of-function (gof) mutation causes ectopic expression of mab-5 in many cells, including QR, and drives posterior migration of the QR descendant AQR (Salser et al 1993;Chapman et al 2008). RNA-mediated interference (RNAi) knockdown of spon-1 partially suppressed posterior AQR migration in mab-5(gof), suggesting that spon-1 mediates the effects of mab-5(gof) in posterior migration (Tamayo et al 2013).…”