Methyl-CpG binding protein 2 （MeCP2） has a crucial role in transcriptional regulation and neural development （Ausi6 et al., 2014）. Loss of function mutations of MECP2 in human lead to Rett syndrome （RTT）, a seve...Methyl-CpG binding protein 2 （MeCP2） has a crucial role in transcriptional regulation and neural development （Ausi6 et al., 2014）. Loss of function mutations of MECP2 in human lead to Rett syndrome （RTT）, a severe neurodevelopmental disorders （Amir et al., 1999）, whereas individuals with the chromosomal duplications containing the MECP2 locus showed severe autism-like symptoms （Ramocki et al., 2009）.展开更多
Dendrites and the dendritic spines of neurons play key roles in the connectivity of the brain and have been recognized as the locus of long-term synaptic plasticity,which is correlated with learning and memory.The dev...Dendrites and the dendritic spines of neurons play key roles in the connectivity of the brain and have been recognized as the locus of long-term synaptic plasticity,which is correlated with learning and memory.The development of dendrites and spines in the mammalian central nervous system is a complex process that requires specific molecular events over a period of time.It has been shown that specific molecules are needed not only at the spine’s point of contact,but also at a distance,providing signals that initiate a cascade of events leading to synapse formation.The specific molecules that act to signal neuronal differentiation,dendritic morphology,and synaptogenesis are tightly regulated by genetic and epigenetic programs.It has been shown that the dendritic spine structure and distribution are altered in many diseases,including many forms of mental retardation(MR),and can also be potentiated by neuronal activities and an enriched environment.Because dendritic spine pathologies are found in many types of MR,it has been proposed that an inability to form normal spines leads to the cognitive and motor deficits that are characteristic of MR.Epigenetic mechanisms,including DNA methylation,chromatin remodeling,and the noncoding RNA-mediated process,have profound regulatory roles in mammalian gene expression.The study of epigenetics focuses on cellular effects that result in a heritable pattern of gene expression without changes to genomic encoding.Despite extensive efforts to understand the molecular regulation of dendrite and spine development,epigenetic mechanisms have only recently been considered.In this review,we will focus on epigenetic mechanisms that regulate the development and maturation of dendrites and spines.We will discuss how epigenetic alterations could result in spine abnormalities that lead to MR,such as is seen in fragile X and Rett syndromes.We will also discuss both general methodology and recent technological advances in the study of neuronal dendrites and spines.展开更多
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB02050400)the National Natural Science Foundation of China(Grant No. #91432111) to Z.Qiu
文摘Methyl-CpG binding protein 2 （MeCP2） has a crucial role in transcriptional regulation and neural development （Ausi6 et al., 2014）. Loss of function mutations of MECP2 in human lead to Rett syndrome （RTT）, a severe neurodevelopmental disorders （Amir et al., 1999）, whereas individuals with the chromosomal duplications containing the MECP2 locus showed severe autism-like symptoms （Ramocki et al., 2009）.
基金This work is supported by grants from the International Rett Syndrome Foundation(IRSF)the NIH(Nos:MH080434 and MH078972).R.D.S.is supported by a Minority Supplement to NIH grant(No.MH080434).
文摘Dendrites and the dendritic spines of neurons play key roles in the connectivity of the brain and have been recognized as the locus of long-term synaptic plasticity,which is correlated with learning and memory.The development of dendrites and spines in the mammalian central nervous system is a complex process that requires specific molecular events over a period of time.It has been shown that specific molecules are needed not only at the spine’s point of contact,but also at a distance,providing signals that initiate a cascade of events leading to synapse formation.The specific molecules that act to signal neuronal differentiation,dendritic morphology,and synaptogenesis are tightly regulated by genetic and epigenetic programs.It has been shown that the dendritic spine structure and distribution are altered in many diseases,including many forms of mental retardation(MR),and can also be potentiated by neuronal activities and an enriched environment.Because dendritic spine pathologies are found in many types of MR,it has been proposed that an inability to form normal spines leads to the cognitive and motor deficits that are characteristic of MR.Epigenetic mechanisms,including DNA methylation,chromatin remodeling,and the noncoding RNA-mediated process,have profound regulatory roles in mammalian gene expression.The study of epigenetics focuses on cellular effects that result in a heritable pattern of gene expression without changes to genomic encoding.Despite extensive efforts to understand the molecular regulation of dendrite and spine development,epigenetic mechanisms have only recently been considered.In this review,we will focus on epigenetic mechanisms that regulate the development and maturation of dendrites and spines.We will discuss how epigenetic alterations could result in spine abnormalities that lead to MR,such as is seen in fragile X and Rett syndromes.We will also discuss both general methodology and recent technological advances in the study of neuronal dendrites and spines.
