title: Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex.
abstract: 14-3-3 proteins are ubiquitously-expressed and multifunctional proteins. There are seven isoforms in mammals with a high level of homology, suggesting potential functional redundancy. We previously found that two of seven isoforms, 14-3-3epsilon and 14-3-3zeta, are important for brain development, in particular, radial migration of pyramidal neurons in the developing cerebral cortex. In this work, we analyzed the function of another isoform, the protein 14-3-3gamma, with respect to neuronal migration in the developing cortex. We found that in utero 14-3-3gamma-deficiency resulted in delays in neuronal migration as well as morphological defects. Migrating neurons deficient in 14-3-3gamma displayed a thicker leading process stem, and the basal ends of neurons were not able to reach the boundary between the cortical plate and the marginal zone. Consistent with the results obtained from in utero electroporation, time-lapse live imaging of brain slices revealed that the ablation of the 14-3-3gamma proteins in pyramidal neurons slowed down their migration. In addition, the 14-3-3gamma deficient neurons showed morphological abnormalities, including increased multipolar neurons with a thicker leading processes stem during migration. These results indicate that the 14-3-3gamma proteins play an important role in radial migration by regulating the morphology of migrating neurons in the cerebral cortex. The findings underscore the pathological phenotypes of brain development associated with the disruption of different 14-3-3 proteins and will advance the preclinical data regarding disorders caused by neuronal migration defects.
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Tomoka
authors: T
authors: Wachi
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Brett
authors: B
authors: Cornell
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Courtney
authors: C
authors: Marshall
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Vladimir
authors: V
authors: Zhukarev
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Peter W
authors: PW
authors: Baas
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, 19129.
authors: Kazuhito
authors: K
authors: Toyo-oka
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency* / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development*; D018274:Electroporation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D001973:Bromodeoxyuridine
keywords: 14-3-3; cerebral cortex; in utero electroporation; neuronal migration; time-lapse live imaging