Loss of MeCP2 causes subtle alteration in dendritic arborization of retinal ganglion cells

Lee, Wooje; Mariappan, Ramesh; De, Koushitak; Ohn, Takbum

doi:10.1080/19768354.2021.1920459

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Interestingly, this phenotype could be rescued with a histone deacetylase 6 (HDAC6) inhibitor suggesting that microtubule instability contributes to the primary cilia deficits observed in these models [48]. Notably, while this study provides strong evidence that support a relationship between MeCP2 function and primary cilia, another study showed that of loss of Mecp2 in mouse retina cells did not affect cilia formation [74]. Taken together, these studies suggest that MeCP2 effect on primary cilia might be cell-type dependent.…”

Section: Rett Syndromementioning

confidence: 65%

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies

Karalis

Donovan

Şahin

2022

JDB

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Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the primary cilium including Sonic Hedgehog (Shh) and Wnt signaling. Therefore, it is no surprise that mutated genes encoding defective proteins that affect primary cilia function or structure are responsible for a group of disorders collectively termed ciliopathies. The severe neurologic abnormalities observed in several ciliopathies have prompted examination of primary cilia structure and function in other brain disorders. Recently, neuronal primary cilia defects were observed in monogenic neurodevelopmental disorders that were not traditionally considered ciliopathies. The molecular mechanisms of how these genetic mutations cause primary cilia defects and how these defects contribute to the neurologic manifestations of these disorders remain poorly understood. In this review we will discuss monogenic neurodevelopmental disorders that exhibit cilia deficits and summarize findings from studies exploring the role of primary cilia in the brain to shed light into how these deficits could contribute to neurologic abnormalities.

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Section: Rett Syndromementioning

confidence: 65%

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies

Karalis

Donovan

Şahin

2022

JDB

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“…Knock-down of KAP1 (TRIM28) in human neural progenitor cells (NPCs) generally upregulates various HERV gene expressions (Brattås et al, 2017). A gene regulatory network based on HERVs may participate in the control of gene expression of protein-coding transcripts necessary for proper development of nervous systems ( Lee et al, 2019b ; 2021b ; Zhang et al, 2019a ).…”

Section: Regulatory Factors For Hervsmentioning

confidence: 99%

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

Durnaoglu

Lee

Ahnn

2021

Molecules and Cells

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The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

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“…However, its expression increases during post-natal stages, where it plays a critical role for neuronal maturation and synaptic pruning ( Johnston et al, 2001 ). MeCP2 levels are high in mature neurons, where it seems to be involved in processes of activity-dependent regulation of gene expression ( Lee et al, 2014 , 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

Torres-Pérez

Martínez-Rodríguez

Forte

et al. 2022

Front. Behav. Neurosci.

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The methyl-CpG binding protein 2 gene (MECP2) encodes an epigenetic transcriptional regulator implicated in neuronal plasticity. Loss-of-function mutations in this gene are the primary cause of Rett syndrome and, to a lesser degree, of other neurodevelopmental disorders. Recently, we demonstrated that both Mecp2 haploinsuficiency and mild early life stress decrease anxiety-like behaviours and neuronal activation in brain areas controlling these responses in adolescent female mice. Here, we extend this work to males by using Mecp2-null and wild type adolescent mice subjected to maternal separation and their non-stressed controls. We assessed their behavioural responses in a battery of anxiety-provoking tests. Upon exposure to an elevated plus maze in aversive conditions, we evaluated changes in c-FOS expression in stress- and anxiety-related brain regions. In addition, we assessed the impact of maternal separation in neuronal maturation using doublecortin and reelin as surrogate markers. Mutant males showed reduced motor abilities, increased activation of the olfactory bulbs, probably due to breathing abnormalities, and decreased activation of the paraventricular thalamic nucleus, when compared to wild type mice. In addition, maternal separation increased the number of immature doublecortin-like neurons found in Mecp2-null animals. Moreover, this work shows for the first time that reelin is decreased in the mutant animals at the olfactory tubercle, piriform cortex and hippocampal dentate gyrus, an effect also associated to maternal separation. Taken together, our results suggest that maternal separation exacerbates some phenotypical alterations associated with lack of MeCP2 in adolescent males.

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Loss of MeCP2 causes subtle alteration in dendritic arborization of retinal ganglion cells

Cited by 3 publications

References 29 publications

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

Early life stress exacerbates behavioural and neuronal alterations in adolescent male mice lacking methyl-CpG binding protein 2 (Mecp2)

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