Excitatory neuronal CHD8 in the regulation of neocortical development and sensory-motor behaviors

Kweon, Hanseul; Jung, Won Beom; Im, Geun Ho; Ryoo, Jia; Lee, Joon Hyuk; Do, Hogyeong; Choi, Yeonsoo; Song, You Hyang; Jung, Hwajin; Park, Haram; Qiu, Lily R.; Ellegood, Jacob; Shim, Hyun Ji; Yang, Esther; Kim, Hyun; Lerch, Jason P.; Lee, Seung Hee; Chung, Won‐Suk; Kim, Daesoo; Kim, Seong Gi; Kim, Eunjoon

doi:10.1016/j.celrep.2021.108780

Cited by 21 publications

(28 citation statements)

References 73 publications

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“…It should be noted that the regulation of synaptic plasticity in part also takes place at the level of regulation of transcription, by processes such as chromatin remodeling, with a central role for the ASD-related genes MECP2 and CHD8 . Established Mecp2 and Chd8 genetic mouse models exist that display ASD-related behavioral phenotypes such as altered sensory responses as well as showing synaptic and brain connectivity deficits [ 39 , 59 , 78 , 92 , 93 ]. Aligned with the synaptic genes discussed in this review, these genes are specifically important during embryonic and early postnatal development in cortico-striatal neuronal circuits; recently, these topics have been elegantly described in detail for Mecp2 and Chd8 by Hoffmann and Spengler et al, 2021; Li and Pozzo-Miller, 2020; Smith et al, 2019, and Varghese et al, 2017 [ 94 , 95 , 96 , 97 ].…”

Section: From Neural Circuit To Targeted Gene-based Therapymentioning

confidence: 99%

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Riemersma

Havekes

Kas

2021

Genes

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

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Section: From Neural Circuit To Targeted Gene-based Therapymentioning

confidence: 99%

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Riemersma

Havekes

Kas

2021

Genes

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“…To decode the information encoded in the neural network, it is important to interpret the communication between neurons. Therefore, the measurements of PSCs have been utilized not only in several studies for the electrophysiological analysis of synaptic transmission in the nervous system [12,14,17], but also for the circuit mechanisms underlying certain types of behaviors [1,13,15]. Consequently, the importance of understanding the neuronal network has led to the development of novel tools to analyze PSC data [4][5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 99%

“…Experimental data were prepared by recording spontaneous inhibitory postsynaptic current (IPSC) in a pyramidal neuron of the medial prefrontal cortex in a mouse. Spontaneous IPSCs were detected by two commonly used analysis tools: MiniAnalysis (Synaptosoft, USA) [1,2,[12][13][14], and Clampfit (Axon Instruments, USA) [15,16].…”

Section: Comparison Of Different Event Detection Methodsmentioning

confidence: 99%

Minhee Analysis Package: an integrated software package for detection and management of spontaneous synaptic events

2021

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To understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.

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“…In general, most CHD proteins are important for chromatin access and gene expression in cell-type specific manner. Although the role of CHDs in neural stem cells and neurodevelopmental process has been well documented [8,13,[15][16][17][18], their regulatory functions in HSPC maintenance and differentiation have only been appreciated recently.…”

Section: Chromodomain Helicase Dna-binding Family Proteinsmentioning

confidence: 99%

Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance

Zheng

2022

Current Opinion in Hematology

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Purpose of review ATP-dependent chromatin remodeling factors utilize energy from ATP hydrolysis to modulate DNA-histone structures and regulate gene transcription. They are essential during hematopoiesis and for hematopoietic stem and progenitor cell (HSPC) function. This review discusses the recently unveiled roles of these chromatin remodelers in HSPC regulation, with an emphasis on the mechanism of chromodomain helicase DNA-binding (CHD) family members. Recent findingsRecent studies of ATP-dependent chromatin remodelers have revealed that individual CHD family members engage in distinct mechanisms in regulating HSPC cell fate. For example, CHD8 is required for HSPC survival by restricting both P53 transcriptional activity and protein stability in steady state hematopoiesis while the related CHD7 physically interacts with RUNX family transcription factor 1 (RUNX1) and suppresses RUNX1-induced expansion of HSPCs during blood development. Moreover, other CHD subfamily members such as CHD1/CHD2 and CHD3/CHD4, as well as the switch/sucrose nonfermentable, imitation SWI, and SWI2/SNF2 related (SWR) families of chromatin modulators, have also been found important for HSPC maintenance by distinct mechanisms.

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Excitatory neuronal CHD8 in the regulation of neocortical development and sensory-motor behaviors

Cited by 21 publications

References 73 publications

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Minhee Analysis Package: an integrated software package for detection and management of spontaneous synaptic events

Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance

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