title: Cadherin 2/4 signaling via PTP1B and catenins is crucial for nucleokinesis during radial neuronal migration in the neocortex.
abstract: Cadherins are crucial for the radial migration of excitatory projection neurons into the developing neocortical wall. However, the specific cadherins and the signaling pathways that regulate radial migration are not well understood. Here, we show that cadherin 2 (CDH2) and CDH4 cooperate to regulate radial migration in mouse brain via the protein tyrosine phosphatase 1B (PTP1B) and α- and β-catenins. Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons. Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted. This defect is partially rescued by overexpression of LIS1, a microtubule-associated protein that has previously been shown to regulate nucleokinesis. Taken together, our findings indicate that cadherin-mediated signaling to the cytoskeleton is crucial for nucleokinesis of neocortical projection neurons during their radial migration.
authors.affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA martinezgarayi@cardiff.ac.uk umueller@scripps.edu.
authors.forename: Isabel
authors.initials: I
authors.lastname: Martinez-Garay
authors.affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Sanz
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA Program of Pediatric Stem Cell Biology, Children's Hospital Colorado, Aurora, CO 80045, USA.
authors.forename: Santos J
authors.initials: SJ
authors.lastname: Franco
authors.affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA martinezgarayi@cardiff.ac.uk umueller@scripps.edu.
authors.forename: Ulrich
authors.identifier: 0000-0003-2736-6494
authors.initials: U
authors.lastname: Mueller
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019579:Neocortex / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000648:ultrastructure; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000199:Actins; D015820:Cadherins; D051177:Catenins; D008869:Microtubule-Associated Proteins; C083970:R-cadherin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: CDH2; Cadherin; Catenin; LIS1; Mouse; Nucleokinesis; Radial migration