The fat-like cadherin CDH-4 acts cell-non-autonomously in anterior-posterior neuroblast migration

Dev Biol. 2014 Aug 15;392(2):141-52. doi: 10.1016/j.ydbio.2014.06.009. Epub 2014 Jun 19.


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.

Keywords: Anterior–posterior; C. elegans; CDH-4/Fat; Neuroblast migration; PTP-3/LAR; UNC-40/DCC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / physiology*
  • Central Nervous System / embryology*
  • Gene Components
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology*
  • Protein Tyrosine Phosphatases
  • Signal Transduction / physiology*


  • CDH-4 protein, C elegans
  • Cadherins
  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Membrane Proteins
  • UNC-40 protein, C elegans
  • PTP-3 protein, C elegans
  • Protein Tyrosine Phosphatases