title: 14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain.
abstract: During brain development, neural progenitor cells proliferate and differentiate into neural precursors. These neural precursors migrate along the radial glial processes and localize at their final destination in the cortex. Numerous reports have revealed that 14-3-3 proteins are involved in many neuronal activities, although their functions in neurogenesis remain unclear. Here, using 14-3-3ε/ζ double knock-out mice, we found that 14-3-3 proteins are important for proliferation and differentiation of neural progenitor cells in the cortex, resulting in neuronal migration defects and seizures. 14-3-3 deficiency resulted in the increase of δ-catenin and the decrease of β-catenin and αN-catenin. 14-3-3 proteins regulated neuronal differentiation into neurons via direct interactions with phosphorylated δ-catenin to promote F-actin formation through a catenin/Rho GTPase/Limk1/cofilin signaling pathway. Conversely, neuronal migration defects seen in the double knock-out mice were restored by phosphomimic Ndel1 mutants, but not δ-catenin. Our findings provide new evidence that 14-3-3 proteins play important roles in neurogenesis and neuronal migration via the regulation of distinct signaling cascades.
authors.affiliation: Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco School of Medicine, San Francisco, California 94143, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, ajw168@case.edu ktoyooka@drexelmed.edu.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Toyo-oka
authors.affiliation: Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco School of Medicine, San Francisco, California 94143, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Wachi
authors.affiliation: Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hunt
authors.affiliation: Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taya
authors.affiliation: Department of Human Immunology, Centre for Cancer Biology, South Australia Pathology, Adelaide, South Australia, Australia, and.
authors.forename: Hayley
authors.initials: H
authors.lastname: Ramshaw
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.affiliation: Department of Human Immunology, Centre for Cancer Biology, South Australia Pathology, Adelaide, South Australia, Australia, and.
authors.forename: Quenten P
authors.initials: QP
authors.lastname: Schwarz
authors.affiliation: Department of Human Immunology, Centre for Cancer Biology, South Australia Pathology, Adelaide, South Australia, Australia, and.
authors.forename: Angel F
authors.initials: AF
authors.lastname: Lopez
authors.affiliation: Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco School of Medicine, San Francisco, California 94143, Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 ajw168@case.edu ktoyooka@drexelmed.edu.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D051177:Catenins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding
chemical_list: D048948:14-3-3 Proteins; D000199:Actins; D051177:Catenins; C000590975:Ywhaz protein, mouse; C576823:Ywhae protein, mouse
keywords: 14-3-3; delta-catenin; neurogenesis; neuronal differentiation; neuronal migration