Overexpression of the 14-3-3gamma protein in embryonic mice results in neuronal migration delay in the developing cerebral cortex.
The 14-3-3 protein family is a group of multifunctional proteins that are highly expressed in the brain; however, their functions in brain development are largely unknown. Williams Syndrome is a neurodevelopmental disorder caused by a deletion in the 7q11.23 chromosome locus, including the gene encoding 14-3-3gamma, resulting in developmental delay, intellectual disabilities and epilepsy. We have previously shown that knocking down the 14-3-3gamma protein in utero in mice results in delays in neuronal migration of pyramidal neurons in the cortex. Importantly, there is a reciprocal duplication syndrome to Williams Syndrome where the 7q11.23 locus is duplicated, resulting in epilepsy and intellectual disabilities. Thus, the deletion or the duplication of the 7q11.23 chromosome locus results in epilepsy. Taken together with the fact that defects in neuronal migration are one of main causes for epilepsy, we analyzed if the overexpression of 14-3-3gamma causes neuronal migration defects. In this work, we found that the overexpression of 14-3-3gamma in utero in the developing mouse cortex results in delays in pyramidal neuron migration, similar to what was previously observed when 14-3-3gamma was knocked down. These results, in conjunction with our previous research, indicate that a balance of 14-3-3gamma expression is required during cortical development to prevent delays in neuronal migration. This work provides clear evidence as to the involvement of 14-3-3gamma in neurodevelopmental disorders and how a disruption in 14-3-3gamma expression may contribute to the neurodevelopmental disorders that manifest when the 7q11.23 locus is altered.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Brett
B
Cornell
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Tomoka
T
Wachi
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Vladimir
V
Zhukarev
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Electronic address: ktoyooka@drexelmed.edu.
Kazuhito
K
Toyo-Oka
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology*
D048948:14-3-3 Proteins
14-3-3; 14-3-3gamma; 7q11.23 duplication; In utero electroporation; Neurodevelopmental defects; Neuronal migration