| Experiment Id | GSE119935 | Name | The Hippo Pathway Prevents YAP/TAZ-Driven Hypertranscription and Controls Neural Progenitor Number [microarray] |
| Experiment Type | transcription profiling by array | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2022-11-17 |
| description | The Hippo pathway controls the activity of YAP/TAZ transcriptional coactivators through a kinase cascade. Despite the critical role of this pathway in tissue growth and tumorigenesis, it is not fully understood how YAP/TAZ-mediated transcription drives proliferation. By analyzing the effects of inactivating LATS1/2 kinases, the direct upstream inhibitors of YAP/TAZ, on mouse brain development and applying cell-number-normalized transcriptome analysis, we discovered that YAP/TAZ activation causes a global increase in transcription activity, known as hypertranscription, and upregulates many genes associated with increased biosynthetic capacity and proliferation. In contrast, conventional read-depth-normalized RNA-sequencing analysis failed to detect the scope of the transcriptome shift and missed most relevant gene ontologies. Hypertranscription in neural progenitors inhibits differentiation and triggers DNA replication stress, DNA damage, and p53 activation, resulting in massive apoptosis. Our findings reveal the remarkable impact of YAP/TAZ activation on global transcription activity and have important implications for understanding YAP/TAZ function We used microarrays to compare the gene expression profiles of cortices from control and Lats1F/F;Lats2F/F;Nestin-Cre double knock-out E12.5 mouse embryos. |
