title: Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord.
abstract: Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration.
  
  
  
  By pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord.
  
  
  
  Netrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.
authors: Department of MCDB, University of Colorado, Boulder, CO, 80309, USA. harald.junge@colorado.edu.
authors: Harald J
authors: HJ
authors: Junge
authors: Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
authors: Andrea R
authors: AR
authors: Yung
authors: Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
authors: Lisa V
authors: LV
authors: Goodrich
authors: Department of MCDB, University of Colorado, Boulder, CO, 80309, USA. zhe.chen@colorado.edu.
authors: Zhe
authors: 0000-0003-0683-9491
authors: Z
authors: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement; D000075389:DCC Receptor; D007395:Interneurons / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D000075388:Netrin-1; D058953:Neural Stem Cells / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013116:Spinal Cord / Q000254:growth & development*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D000075389:DCC Receptor; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C501910:Dcc protein, mouse; C000617353:Ntn1 protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins
keywords: DCC; Netrin1; Neuronal migration; ROBO3; Spinal cord neurons