title: The fat-like cadherin CDH-4 acts cell-non-autonomously in anterior-posterior neuroblast migration.
abstract: Directed migration of neurons is critical in the normal and pathological development of the brain and central nervous system. In Caenorhabditis elegans, the bilateral Q neuroblasts, QR on the right and QL on the left, migrate anteriorly and posteriorly, respectively. Initial protrusion and migration of the Q neuroblasts is autonomously controlled by the transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21. As QL migrates posteriorly, it encounters and EGL-20/Wnt signal that induces MAB-5/Hox expression that drives QL descendant posterior migration. QR migrates anteriorly away from EGL-20/Wnt and does not activate MAB-5/Hox, resulting in anterior QR descendant migration. A forward genetic screen for new mutations affecting initial Q migrations identified alleles of cdh-4, which caused defects in both QL and QR directional migration similar to unc-40, ptp-3, and mig-21. Previous studies showed that in QL, PTP-3/LAR and MIG-21 act in a pathway in parallel to UNC-40/DCC to drive posterior QL migration. Here we show genetic evidence that CDH-4 acts in the PTP-3/MIG-21 pathway in parallel to UNC-40/DCC to direct posterior QL migration. In QR, the PTP-3/MIG-21 and UNC-40/DCC pathways mutually inhibit each other, allowing anterior QR migration. We report here that CDH-4 acts in both the PTP-3/MIG-21 and UNC-40/DCC pathways in mutual inhibition in QR, and that CDH-4 acts cell-non-autonomously. Interaction of CDH-4 with UNC-40/DCC in QR but not QL represents an inherent left-right asymmetry in the Q cells, the nature of which is not understood. We conclude that CDH-4 might act as a permissive signal for each Q neuroblast to respond differently to anterior-posterior guidance information based upon inherent left-right asymmetries in the Q neuroblasts.
authors: Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, United States.
authors: Lakshmi
authors: L
authors: Sundararajan
authors: Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, United States.
authors: Megan L
authors: ML
authors: Norris
authors: Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, United States.
authors: Sebastian
authors: S
authors: Schöneich
authors: Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, United States.
authors: Brian D
authors: BD
authors: Ackley
authors: Programs in Genetics and Molecular, Cellular, and Developmental Biology, Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, United States. Electronic address: erikl@ku.edu.
authors: Erik A
authors: EA
authors: Lundquist
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology*; D040461:Gene Components; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C528530:CDH-4 protein, C elegans; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C102174:UNC-40 protein, C elegans; C581335:PTP-3 protein, C elegans; D017027:Protein Tyrosine Phosphatases
keywords: Anterior–posterior; C. elegans; CDH-4/Fat; Neuroblast migration; PTP-3/LAR; UNC-40/DCC