<scp>TCF</scp>
            20 dysfunction leads to cortical neurogenesis defects and autistic‐like behaviors in mice

Feng, Chao; Zhao, Jianfeng; Ji, Fen; Su, Lihe; Chen, Yihui; Jiao, Jianwei

doi:10.15252/embr.201949239

Cited by 23 publications

(31 citation statements)

References 50 publications

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“…Rai1 mutant mouse models display many SMS-like symptoms including obesity, motor dysfunction, and learning and memory deficits ( 66 – 68 ). Similarly, our Tcf20 +/− mice recapitulate the core TAND features, as does another Tcf20 +/− allele ( 69 ). The clinical features of patients with PHF14 mutations—such as intellectual disability, autistic behaviors, speech delay or loss, sleep disturbance, motor incoordination, and regression—were also seen in TAND and RTT patients ( SI Appendix , Fig.…”

Section: Discussionsupporting

confidence: 64%

Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders

Zhou

Hamdan

Yalamanchili

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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MeCP2 is associated with Rett syndrome (RTT), MECP2 duplication syndrome, and a number of conditions with isolated features of these diseases, including autism, intellectual disability, and motor dysfunction. MeCP2 is known to broadly bind methylated DNA, but the precise molecular mechanism driving disease pathogenesis remains to be determined. Using proximity-dependent biotinylation (BioID), we identified a transcription factor 20 (TCF20) complex that interacts with MeCP2 at the chromatin interface. Importantly, RTT-causing mutations in MECP2 disrupt this interaction. TCF20 and MeCP2 are highly coexpressed in neurons and coregulate the expression of key neuronal genes. Reducing Tcf20 partially rescued the behavioral deficits caused by MECP2 overexpression, demonstrating a functional relationship between MeCP2 and TCF20 in MECP2 duplication syndrome pathogenesis. We identified a patient exhibiting RTT-like neurological features with a missense mutation in the PHF14 subunit of the TCF20 complex that abolishes the MeCP2–PHF14–TCF20 interaction. Our data demonstrate the critical role of the MeCP2–TCF20 complex for brain function.

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Section: Discussionsupporting

confidence: 64%

Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders

Zhou

Hamdan

Yalamanchili

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Additionally, TCF mutations have been found in ASD patients. TCF20 KO impairs neurogenesis and induces autistic‐like (Feng et al., 2020)behavior in mice, that can be rescued by overexpressing TCF4 (Feng et al., 2020). These studies suggest a direct link between Wnt‐signaling and ASD‐like behavior in autism mouse models.…”

Section: Wnt / β‐Catenin and Shh Signaling Pathways In Asdmentioning

confidence: 99%

Potential crosstalk between sonic hedgehog‐WNT signaling and neurovascular molecules: Implications for blood–brain barrier integrity in autism spectrum disorder

Gozal

Jagadapillai

Cai

et al. 2021

Journal of Neurochemistry

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disease originating from combined genetic and environmental factors. Post‐mortem human studies and some animal ASD models have shown brain neuroinflammation, oxidative stress, and changes in blood–brain barrier (BBB) integrity. However, the signaling pathways leading to these inflammatory findings and vascular alterations are currently unclear. The BBB plays a critical role in controlling brain homeostasis and immune response. Its dysfunction can result from developmental genetic abnormalities or neuroinflammatory processes. In this review, we explore the role of the Sonic Hedgehog/Wingless‐related integration site (Shh/Wnt) pathways in neurodevelopment, neuroinflammation, and BBB development. The balance between Wnt‐β‐catenin and Shh pathways controls angiogenesis, barriergenesis, neurodevelopment, central nervous system (CNS) morphogenesis, and neuronal guidance. These interactions are critical to maintain BBB function in the mature CNS to prevent the influx of pathogens and inflammatory cells. Genetic mutations of key components of these pathways have been identified in ASD patients and animal models, which correlate with the severity of ASD symptoms. Disruption of the Shh/Wnt crosstalk may therefore compromise BBB development and function. In turn, impaired Shh signaling and glial activation may cause neuroinflammation that could disrupt the BBB. Elucidating how ASD‐related mutations of Shh/Wnt signaling could cause BBB leaks and neuroinflammation will contribute to our understanding of the role of their interactions in ASD pathophysiology. These observations may provide novel targeted therapeutic strategies to prevent or alleviate ASD symptoms while preserving normal developmental processes. Cover Image for this issue: https://doi.org/10.1111/jnc.15081

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“…TCF20 is essential for neurogenesis and is ubiquitously expressed in the developing cerebral cortex, notably in neural stem cells of mouse embryos. 16 Particularly, TCF20 knockout mice lead to neurogenesis defects with imbalanced differentiation and proliferation of neural progenitor cells and leads to autistic-like behaviors in mice.…”

Section: Microarray Resultsmentioning

confidence: 99%

Rare and de novo duplications containing TCF20 are associated with a neurodevelopmental disorder

et al. 2021

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Transcriptor co-activator factor 20 gene (TCF20) encodes a nuclear chromatin-binding protein involved in regulation of gene expression. In human pathology, pathogenic variants or deletions in TCF20 were identified in patients with developmental delay, variable intellectual disability and behavioral impairment (OMIM: 618430). The shared core phenotype includes developmental delay, hypotonia, motor delay, autism spectrum disorders, neurobehavioral anomalies, neurological features such as ataxia, seizures, movement disorders, structural brain anomalies, craniofacial features and various congenital anomalies. Most pathogenic variants are loss-of-function variants. Duplication including TCF20 was suspected to cause a neurodevelopmental disorder (NDD) with mirror traits compared to patients with TCF20 deletions. In the present study, we report three patients from three unrelated families with NDD with a de novo duplication at 22q13.2 encompassing TCF20. We propose that the TCF20 duplication could be involved in a new 22q13.2 microduplication syndrome with high penetrance, enlarging the genotype-phenotype knowledge of TCF20-associated NDDs.

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TCF 20 dysfunction leads to cortical neurogenesis defects and autistic‐like behaviors in mice

Cited by 23 publications

References 50 publications

Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders

Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders

Potential crosstalk between sonic hedgehog‐WNT signaling and neurovascular molecules: Implications for blood–brain barrier integrity in autism spectrum disorder

Rare and de novo duplications containing TCF20 are associated with a neurodevelopmental disorder

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