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FASEB J. 2015 Dec;29(12):5059-71. doi: 10.1096/fj.15-275651. Epub 2015 Aug 18.

Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo.

Author information

1
*Department of Psychiatry and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
2
*Department of Psychiatry and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA amelia.eisch@utsouthwestern.edu jenny.hsieh@utsouthwestern.edu.

Abstract

Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity-dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a, -c, and -d were inducibly deleted in adult nestin-expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not. Based on this expression, we hypothesized that Mef2a, -c, and -d deletion in adult nestin-expressing NSPCs and their progeny would result in fewer mature neurons. Control mice revealed an increase in YFP(+) neurons and dendrite formation over time. Contrary to our hypothesis, inducible Mef2 KO mice also displayed an increase in YFP(+) neurons over time-but with significantly stunted dendrites-suggesting an uncoupling of neuron survival and dendritogenesis. We also found non-cell-autonomous effects after Mef2a, -c, and -d deletion. These in vivo findings indicate a surprising functional role for Mef2a, -c, and -d in cell- and non-cell-autonomous control of adult hippocampal neurogenesis that is distinct from its role during development.

KEYWORDS:

dentate gyrus; doublecortin; hippocampus; transcription factor; transgenic mouse

PMID:
26286136
PMCID:
PMC4653059
DOI:
10.1096/fj.15-275651
[Indexed for MEDLINE]
Free PMC Article

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