Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation

Lyons, GE; Micales, BK; Schwarz, John J.; Martin, J. A.; Olson, E. B.

doi:10.1523/jneurosci.15-08-05727.1995

Cited by 257 publications

(210 citation statements)

References 30 publications

Supporting

Mentioning

200

Contrasting

Unclassified

Order By: Relevance

“…SNPs were classified as derived according to the method described by Green et al (2010). ( known regulators of activity-dependent synaptic development programs, such as MEF2A (Lyons et al 1995;Flavell et al 2006;Shalizi et al 2006). MEF2A plays multiple roles in neuronal development, including neuronal survival (Mao et al 1999;Shalizi et al 2003), dendritic differentiation (Shalizi et al 2006), synaptic density of hippocampal neurons (Flavell et al 2006;Barbosa et al 2008), spine density in nucleus accumbens (Pulipparacharuvil et al 2008), and both synapse weakening/elimination and synaptic strengthening (Flavell et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Liu¹,

Somel²,

Tang³

et al. 2012

Genome Res.

218

216

View full text Add to dashboard Cite

Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages.

show abstract

Section: Discussionmentioning

confidence: 99%

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Liu¹,

Somel²,

Tang³

et al. 2012

Genome Res.

218

216

View full text Add to dashboard Cite

show abstract

“…In the adult brain of human and rodent, MEF2C is highly expressed in the regions closely associated with learning and memory, for instance, frontal cortex, entorhinal cortex, dentate gyrus, and amygdala (Leifer et al 1994;Lyons et al 1995). Recently, MEF2 is reported to be a central transcriptional component of the innate immune response in the adult fly (Clark et al 2013).…”

Section: Mef2cmentioning

confidence: 99%

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Zhang

et al. 2015

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a complex agerelated neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease. After three decades of genetic study in AD, dozens of loci harboring genetic variants influencing inflammatory pathways in AD patients has been identified through genome-wide association studies (GWAS). The most well-known GWAS risk factor that is responsible for immune response and inflammation in AD development should be APOE e4 allele. However, a growing number of other GWAS risk AD candidate genes in inflammation have recently been discovered. In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.

show abstract

“…MEF2C is a member of the family of transcription factor MEF2 (Kato et al, 1997;Marinissen et al, 1999) and is highly expressed in developing and adult brain (Leifer et al, , 1994McDermott et al, 1993;Lyons et al, 1995). Activation of ERK5 leads to phosphorylation and therefore enhanced transactivation capacity of MEF2C (Yang et al, 1998).…”

Section: Erk5 Signaling and Suicide Y Dwivedi Et Almentioning

confidence: 99%

Aberrant Extracellular Signal-Regulated Kinase (ERK) 5 Signaling in Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Extracellular signal-regulated kinase 5 (ERK5), the newest member of the mitogen-activated protein (MAP) kinase family, is regulated differently than the other MAP kinases. Emerging evidence suggest the role of ERK5 signaling in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. The present study investigates whether suicide brain is associated with alterations in components of the ERK5 signaling cascade. In the prefrontal cortex (PFC) and hippocampus of suicide subjects (n ¼ 28) and nonpsychiatric control subjects (n ¼ 21), we examined the catalytic activities and protein levels of ERK5 and upstream MAP kinase kinase MEK5 in various subcellular fractions; mRNA levels of ERK5 in total RNA; and DNA-binding activity of myocyte enhancer factor (MEF)2C, a substrate of ERK5. In the hippocampus of suicide subjects, we observed that catalytic activity of ERK5 was decreased in cytosolic and nuclear fractions, whereas catalytic activity of MEK5 was decreased in the total fraction. Further, decreased mRNA and protein levels of ERK5, but no change in protein level of MEK5 were noted. A decrease in MEF2C-DNA-binding activity in the nuclear fraction was also observed. No significant alterations were noted in the PFC of suicide subjects. The observed changes were not related to a specific psychiatric diagnosis. Our findings of reduced activation and/or expression of ERK5 and MEK5, and reduced MEF2C-DNAbinding activity demonstrate abnormalities in ERK5 signaling in hippocampus of suicide subjects and suggest possible involvement of this aberrant signaling in pathogenic mechanisms of suicide.

show abstract

Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation

Cited by 257 publications

References 30 publications

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Aberrant Extracellular Signal-Regulated Kinase (ERK) 5 Signaling in Hippocampus of Suicide Subjects

Contact Info

Product

Resources

About