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Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.

ABSTRACT: Emerging evidence suggests that myocyte enhancer factor 2 (MEF2) transcription factors act as effectors of neurogenesis in the brain, with MEF2C the predominant isoform in developing cerebrocortex. Here, we show that conditional knockout of Mef2c in nestin-expressing neural stem/progenitor cells (NSCs) impaired neuronal differentiation in vivo, resulting in aberrant compaction and smaller somal size. NSC proliferation and survival were not affected. Conditional null mice surviving to adulthood manifested more immature electrophysiological network properties and severe behavioral deficits reminiscent of Rett syndrome, an autism-related disorder. Our data support a crucial role for MEF2C in programming early neuronal differentiation and proper distribution within the layers of the neocortex.

SUBMITTER: Li H

PROVIDER: S-EPMC2453715 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.

Li Hao H Radford Jonathan C JC Ragusa Michael J MJ Shea Katherine L KL McKercher Scott R SR Zaremba Jeffrey D JD Soussou Walid W Nie Zhiguo Z Kang Yeon-Joo YJ Nakanishi Nobuki N Okamoto Shu-ichi S Roberts Amanda J AJ Schwarz John J JJ Lipton Stuart A SA

Proceedings of the National Academy of Sciences of the United States of America 20080701 27

Emerging evidence suggests that myocyte enhancer factor 2 (MEF2) transcription factors act as effectors of neurogenesis in the brain, with MEF2C the predominant isoform in developing cerebrocortex. Here, we show that conditional knockout of Mef2c in nestin-expressing neural stem/progenitor cells (NSCs) impaired neuronal differentiation in vivo, resulting in aberrant compaction and smaller somal size. NSC proliferation and survival were not affected. Conditional null mice surviving to adulthood m ...[more]

PMID: 18599437

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Project description:IntroductionExercise therapies during rehabilitation significantly promote recovery from various deficits after cerebral infarction, which is mediated by neuronal plasticity with distinct inputs. Although adult neurogenesis can also be modulated by neuronal activity before synaptogenesis, how distinct exercises contribute to the neurological reorganization of the injured cerebral cortex remains unclear. In the present study, we aimed to elucidate the effects of different exercise therapies on motor recovery and neuronal reorganization after photochemically induced focal cerebral infarction.MethodsHere, we examined the effects of three different exercises-(a) forced lower-intensity and (b) higher-intensity treadmill exercises, and (c) voluntary exercise with wheel running-on motor recovery and adult neurogenesis in a rat model of focal cerebral infarction. Photochemically induced thrombosis (PIT) was used to generate focal infarction in rats that was mostly confined to their motor cortices.ResultsBeam walking tests showed that recovery after PIT-induced cortical infarction differed in acute and chronic stages and was influenced by the type of exercise. Furthermore, forced low-intensity training had more positive effects on functional recovery than other exercises or control. To evaluate the production of newly generated cells including de novo neurogenesis, we performed lineage analysis with BrdU labeling and immunofluorescence experiments. Lower-intensity treadmill exercise increased the number of BrdU/NeuN colabeled cells, but not total BrdU-retaining or BrdU/Sox2-colabeled cells, in the peri-infarct region of the ipsilateral cortex. In contrast, high-intensity treadmill or voluntary exercises had the opposite effects.ConclusionsThese results suggest that neuronal maturation can be differently modulated by distinct exercises and that low-intensity treadmill exercise could result in more potent generation of mature neurons. This also suggests the possibility that the generation of neural stem/progenitor cells and differentiation might be modulated by rehabilitation-mediated neural plasticity.

Dataset Information

Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.

Publications

Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.

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