Neuronal Myocyte-Specific Enhancer Factor 2D (MEF2D) Is Required for Normal Circadian and Sleep Behavior in Mice
| Autor: | Makito Sato, Masashi Yanagisawa, Eric N. Olson, Jennifer A. Mohawk, Kimberly H. Cox, Joseph S. Takahashi, Seung Hee Yoo |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mef2 Male Sleep Wake Disorders animal structures Light Period (gene) Circadian clock CLOCK Proteins Endogeny Biology Motor Activity 03 medical and health sciences Mice 0302 clinical medicine Animals Circadian rhythm Enhancer Research Articles Mice Knockout Behavior Animal Suprachiasmatic nucleus MEF2 Transcription Factors General Neuroscience Circadian Rhythm PER2 Mice Inbred C57BL 030104 developmental biology RNA Suprachiasmatic Nucleus Sleep Neuroscience 030217 neurology & neurosurgery |
| Popis: | The transcription factor, myocyte enhancer factor-2 (MEF2), is required for normal circadian behavior inDrosophila; however, its role in the mammalian circadian system has not been established. Of the four mammalianMef2genes,Mef2dis highly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, a region critical for coordinating peripheral circadian clocks. Using both conventional and brain-specificMef2dKO (Mef2d−/−) mouse lines, we demonstrate that MEF2D is essential for maintaining the length of the circadian free-running period of locomotor activity and normal sleep patterns in male mice. CrossingMef2d−/−withPer2::lucreporter mice, we show that these behavioral changes are achieved without altering the endogenous period of the master circadian oscillator in the SCN. Together, our data suggest that alterations in behavior inMef2d−/−mice may be the result of an effect on SCN output, rather than an effect on timekeeping within the SCN itself. These findings add to the growing body of evidence that MEF2 proteins play important roles in the brain.SIGNIFICANCE STATEMENTThese studies are the first to show a role for MEF2 proteins in the brain outside of the hippocampus, and our findings suggest that these proteins may play diverse roles in the CNS. It is important to continue to build on our understanding of the roles of proteins acting in the SCN because SCN dysfunction underlies jet lag in humans and influences the response to shift work schedules, which are now known as risk factors for the development of cancer. Our work on MEF2D could be the basis for opening new lines of research in the development and regulation of circadian rhythms. |
| Databáze: | OpenAIRE |
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