TY - JOUR
T1 - Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo
AU - Latchney, Sarah E.
AU - Jiang, Yindi
AU - Petrik, David P.
AU - Eisch, Amelia J
AU - Hsieh, Jenny
N1 - Funding Information:
The authors thank Dr. E. Olson (University of Texas Southwestern Medical Center, Dallas, TX, USA) for providing the Mef2af/f, Mef2cf/f, and Mef2df/f mice. This work was funded by grants from the U.S. National Institutes of Health (NIH) National Institute on Drug Abuse (016765, 023555), the NIH National Institute of Mental Health (107945), the U.S. National Aeronautics and Space Administration (NNX12AB55G, NNX15AE09G) (all to A.J.E.), and grants from the NIH National Institute on Aging (032383, 041815), the NIH National Institute of Neurological Disorders and Stroke (076775, 038572, 081203), the Welch Foundation (I-1660), and the Texas Institute for Brain Injury and Repair (all to J.H.). S.E.L. was supported by an institutional training grant from NIH National Institute on Drug Abuse (T32DA00722; Principle Investigator, A.J.E.).
Publisher Copyright:
© FASEB.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Dentate gyrus
KW - Doublecortin
KW - Hippocampus
KW - Transcription factor
KW - Transgenic mouse
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U2 - 10.1096/fj.15-275651
DO - 10.1096/fj.15-275651
M3 - Article
C2 - 26286136
AN - SCOPUS:84973530974
SN - 0892-6638
VL - 29
SP - 5059
EP - 5071
JO - FASEB Journal
JF - FASEB Journal
IS - 12
ER -