AUTHOR=Keidar Liraz , Gerlitz Gabi , Kshirsagar Aditya , Tsoory Michael , Olender Tsviya , Wang Xing , Yang Ying , Chen Yu-Sheng , Yang Yun-Gui , Voineagu Irina , Reiner Orly 

TITLE=Interplay of LIS1 and MeCP2: Interactions and Implications With the Neurodevelopmental Disorders Lissencephaly and Rett Syndrome

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00370

DOI=10.3389/fncel.2019.00370

ISSN=1662-5102

ABSTRACT=<p><italic>LIS1</italic> is the main causative gene for lissencephaly, while <italic>MeCP2</italic> 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, <italic>Lis1</italic>±, <italic>MeCP2−/y</italic>, 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.</p>