Gene regulatory mechanisms underlying sex differences in brain development and psychiatric disease

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls.

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Does Nutrition during Infancy and Early Childhood Contribute to Later Obesity via Metabolic Imprinting of Epigenetic Gene Regulatory Mechanisms?

Nestlé Nutrition Workshop Series: Pediatric Program - Feeding during Late Infancy and Early Childhood: Impact on Health ◽

10.1159/000086298 ◽

2005 ◽

pp. 157-174 ◽

Cited By ~ 21

Author(s):

Robert A. Waterland

Keyword(s):

Early Childhood ◽

Regulatory Mechanisms ◽

Metabolic Imprinting ◽

Gene Regulatory ◽

Infancy And Early Childhood

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Diverse gene regulatory mechanisms mediated by Polycomb group proteins during neural development

Current Opinion in Neurobiology ◽

10.1016/j.conb.2019.07.003 ◽

2019 ◽

Vol 59 ◽

pp. 164-173 ◽

Cited By ~ 5

Author(s):

Masafumi Tsuboi ◽

Yusuke Hirabayashi ◽

Yukiko Gotoh

Keyword(s):

Neural Development ◽

Polycomb Group ◽

Regulatory Mechanisms ◽

Polycomb Group Proteins ◽

Gene Regulatory

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MEIS2C and MEIS2D promote tumor progression via Wnt/β-catenin and hippo/YAP signaling in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1417-3 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 3

Author(s):

Lei Guan ◽

Ting Li ◽

Nanping Ai ◽

Wei Wang ◽

Bing He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chromatin Immunoprecipitation ◽

Nuclear Translocation ◽

Hippo Pathway ◽

Therapeutic Strategies ◽

Regulatory Mechanisms ◽

Migration And Invasion ◽

Gene Regulatory

Abstract Background MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies. Methods The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2. Results The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status. Conclusions Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.

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