Notch-Mediated Suppression of TSC2 Expression Regulates Cell Differentiation in the Drosophila Intestinal Stem Cell Lineage
Figure 7
Model for TSC–mediated regulation of cell differentiation in the ISC lineage.
Our results identify transcriptional repression of TSC2 as a required step in the induction of EC differentiation by the Notch signaling pathway. This regulation integrates with Insulin-mediated repression of TSC2 function to promote EC growth and endoreplication. Under conditions of low Notch activation, TSC2 expression in EBs remains high and prevents growth of cells differentiating into EE cells. Similarly, in ISCs, high TSC2 expression serves as a ‘buffer’ from nutritional changes that increase IIS activity or can otherwise activate the TOR pathway, thus promoting ISC maintenance.