期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2019.00370
关键词
lissencephaly; Rett syndrome; LIS1; MeCP2; genetic interactions
资金
- Israel Science Foundation [347/15]
- Legacy Heritage Biomedical Program of the Israel Science Foundation [2041/16]
- ISF-NSFC joint research program [2449/16, 31661143034]
- Canadian Institutes of Health Research (CIHR) [2397/18]
- International Development Research Centre (IDRC)
- Israel Science Foundation (ISF)
- IMOH [3-0000-12276]
- German-Israeli Foundation (GIF) [I-1476-203.13/2018]
- United States - Israel Binational Science Foundation (BSF) [2017006]
- Nella and Leon Benoziyo Center for Neurological Diseases
- Jeanne and Joseph Nissim Foundation for Life Sciences Research
- Wohl Biology Endowment Fund
- Lulu P. and David J. Levidow Fund for Alzheimer's Diseases and Neuroscience Research
- Helen and Martin Kimmel Stem Cell Research Institute
- Kekst Family Institute for Medical Genetics
- David and Fela Shapell Family Center for Genetic Disorders Research
- Roberto Kaminitz
LIS1 is the main causative gene for lissencephaly, while MeCP2 is the main causative gene for Rett syndrome, both of which are neurodevelopmental diseases. Here we report nuclear functions for LIS1 and identify previously unrecognized physical and genetic interactions between the products of these two genes in the cell nucleus, that has implications on MeCP2 organization, neuronal gene expression and mouse behavior. Reduced LIS1 levels affect the association of MeCP2 with chromatin. Transcriptome analysis of primary cortical neurons derived from wild type, Lis1 +/-, MeCP2-/y, or double mutants mice revealed a large overlap in the differentially expressed (DE) genes between the various mutants. Overall, our findings provide insights on molecular mechanisms involved in the neurodevelopmental disorders lissencephaly and Rett syndrome caused by dysfunction of LIS1 and MeCP2, respectively.
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