@article{969e76ff7629426da0b3cd4ceb4a673a,
title = "Partially overlapping guidance pathways focus the activity of UNC-40/DCC along the anteroposterior axis of polarizing neuroblasts",
abstract = "Directional migration of neurons and neuronal precursor cells is a central process in nervous system development. In the nematode Caenorhabditis elegans, the two Q neuroblasts polarize and migrate in opposite directions along the anteroposterior body axis. Several key regulators of Q cell polarization have been identified, including MIG-21, DPY-19/DPY19L1, the netrin receptor UNC-40/DCC, the Fat-like cadherin CDH-4 and CDH-3/Fat, which we describe in this study. How these different transmembrane proteins act together to direct Q neuroblast polarization and migration is still largely unknown. Here, we demonstrate that MIG-21 and DPY-19, CDH-3 and CDH-4, and UNC-40 define three distinct pathways that have partially redundant roles in protrusion formation, but also separate functions in regulating protrusion direction. Moreover, we show that the MIG-21, DPY-19 and Fat-like cadherin pathways control the localization and clustering of UNC-40 at the leading edge of the polarizing Q neuroblast, and that this is independent of the UNC-40 ligands UNC-6/netrin and MADD-4. Our results provide insight into a novel mechanism for ligand-independent localization of UNC-40 that directs the activity of UNC-40 along the anteroposterior axis.",
keywords = "Caenorhabditis elegans, DPY-19, Fat-like cadherin, MIG-21, Netrin, Polarization, Q neuroblast, UNC-40/DCC",
author = "Annabel Ebbing and Middelkoop, {Teije C.} and Betist, {Marco C.} and Eduard Bodewes and Korswagen, {Hendrik C.}",
note = "Funding Information: We thank members of the Korswagen group for critically reading the manuscript, the Hubrecht Imaging Center (HIC) for assistance with microscopy and the Utrecht University Gene Editing Facility for recombinant SpCas9 protein. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). Funding Information: We thank members of the Korswagen group for critically reading the manuscript, the Hubrecht Imaging Center (HIC) for assistance with microscopy and the Utrecht University Gene Editing Facility for recombinant SpCas9 protein. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was funded by the research program 14NOISE01 of the Foundation for Fundamental Research on Matter (FOM), which is financially supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). Funding Information: This work was funded by the research program 14NOISE01 of the Foundation for Fundamental Research on Matter (FOM), which is financially supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd",
year = "2019",
month = sep,
day = "25",
doi = "10.1242/dev.180059",
language = "English",
volume = "146",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "18",
}