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

Sarah E. Latchney, Yindi Jiang, David P. Petrik, Amelia J Eisch, Jenny Hsieh

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5059-5071
Number of pages13
JournalFASEB Journal
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Nestin
Neurogenesis
Stem cells
Neurons
Stem Cells
Neural Stem Cells
Dendrites
MEF2 Transcription Factors
Proteins
Transgenic Mice
Brain
Transcription Factors
Cells

Keywords

  • Dentate gyrus
  • Doublecortin
  • Hippocampus
  • Transcription factor
  • Transgenic mouse

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo. / Latchney, Sarah E.; Jiang, Yindi; Petrik, David P.; Eisch, Amelia J; Hsieh, Jenny.

In: FASEB Journal, Vol. 29, No. 12, 01.12.2015, p. 5059-5071.

Research output: Contribution to journalArticle

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