GSE162750
TBL1XR1 ensures balanced neural developmental through NCOR complex-mediated regulation of the MAPK pathway
TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological  aspects. The relative protein is involved in regulation of important cellular pathways and master  regulators of transcriptional output including nuclear receptor repressors, Wnt signaling, and MECP2  protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been  experimentally studied in neurological context, leaving a lack of knowledge in the mechanisms at the  basis of the diseases. We show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal  abnormalities. Either the absence of TBL1XR1, or point mutations interfering with  stability/regulation of NCOR complex induced decreased proliferation and increased differentiation  in neural progenitors. We suggest that this developmental unbalance is due to the failure in the  regulation of MAPK cascade. Together, our results broaden the molecular and functional aftermath  of TBL1XR1 deficiency associated with human disorders. Overall design: 3x Tbl1xr1 flox/flox NSCs infected with Cre, 3x Tbl1xr1 flox/flox NSCs infected with GFP