Myocyte Enhancer Factor 2c Regulates Dendritic Complexity and Connectivity of Cerebellar Purkinje Cells.

Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE

Original Publication: Clifton, NJ : Humana Press, c1987-

Cerebellum/*cytology ; Dendrites/*metabolism ; Nerve Net/*metabolism ; Purkinje Cells/*metabolism; Animals ; Animals, Newborn ; Dendritic Spines/metabolism ; MEF2 Transcription Factors/genetics ; MEF2 Transcription Factors/metabolism ; Mice, Inbred C57BL ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Vesicular Glutamate Transport Protein 1/metabolism ; Vesicular Glutamate Transport Protein 2/metabolism

Mef2c haploinsufficiency is implicated in behavioral deficits related to autism, schizophrenia, and intellectual disability. Although perturbations in the cerebellum, notably Purkinje cells, have been linked to these neurological disorders, the underlying mechanisms remain poorly understood. In this study, we investigated the roles of Mef2c in cerebellar Purkinje cells during the first three weeks of postnatal development. Our analysis revealed that in comparison to other members of the Mef2 family, Mef2c expression is limited to postnatal Purkinje cells. Because the role of Mef2c has not been assessed in GABAergic neurons, we set out to determine the functional significance of Mef2c by knocking down the expression of Mef2c selectively in Purkinje cells. We found that the loss of Mef2c expression during the first and second postnatal week results in an increase in dendritic arborization without impact on the general growth and migration of Purkinje cells. The influence of Mef2c on dendritic arborization persists throughout the first three weeks, but is most prominent during the first postnatal week suggesting a critical period of Mef2c activity. Additionally, the loss of Mef2c expression results in an increase in the number of spines accompanied by an increase in Gad67 and vGluT1 puncta and decrease in vGluT2 puncta. Thus, our results reveal the specific expression and functional relevance of Mef2c in developing Purkinje cells and offer insight to how disruption of the expression of Mef2c in a GABAergic neuronal subtype may lead to pathogenesis of cerebellar-associated disorders.

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RG124/15 Ministry of Education - Singapore

Keywords: Cerebellum; Dendrites; GABAergic neurons; Mef2c; Purkinje cells; Spines

0 (MEF2 Transcription Factors)
0 (Mef2c protein, mouse)
0 (RNA, Messenger)
0 (Vesicular Glutamate Transport Protein 1)
0 (Vesicular Glutamate Transport Protein 2)

Date Created: 20181003 Date Completed: 20190829 Latest Revision: 20210109

20221213

PMC6505522

10.1007/s12035-018-1363-7

30276662