Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo.
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.
*Department of Psychiatry and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Sarah E
SE
Latchney
*Department of Psychiatry and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Yindi
Y
Jiang
*Department of Psychiatry and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
David P
DP
Petrik
*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.
Amelia J
AJ
Eisch
*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.
Jenny
J
Hsieh
D000818:Animals; D003712:Dendrites; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D064231:Nestin / Q000378:metabolism*; D055495:Neurogenesis; D013234:Stem Cells / Q000378:metabolism*
D064231:Nestin
dentate gyrus; doublecortin; hippocampus; transcription factor; transgenic mouse