Research News
Dr. Rongwen Xi's paper identified a master repressor of EE cell specification in Drosophila ISC lineages.
On Aug. 10, 2015, Studies from Dr. Rongwen Xi's laboratory at National Institute of Biological Sciences (NIBS), Beijing, published an online paper titled " Ttk69 acts as a master repressor of enteroendocrine cell specification in Drosophila intestinal stem cell lineages" on Development.
In adult Drosophila midgut, intestinal stem cells (ISCs) periodically produces progenitor cells that undergo a binary fate choice determined primarily by the levels of Notch activity they receive, before terminally differentiate into enterocytes (ECs) or enteroendocrine cells (EEs). Here we identified Ttk69, a BTB domain-containing transcriptional repressor, as a master repressor of EE cell specification in the ISC lineages. Depletion of ttk69 in progenitor cells induces ISC proliferation and rendered all committed progenitor cells to adopt EE cell specification, leading to the production of supernumerary EE cells in the intestinal epithelium. Conversely, forced expression of Ttk69 in progenitor cells was sufficient to prevent EE cell specification. The expression of Ttk69 was not regulated by Notch signaling, and forced activation of Notch, which is sufficient to induce EC specification of normal progenitor cells, failed to prevent EE cell specification of Ttk69-depleted progenitor cells. We found that loss of Ttk69 led to derepression of acheate-scutecomplex (AS-C) genes scute and asense, which then induced prospero expression to promote EE cell specification. These studies suggest that Ttk69 functions in parallel with Notch signaling and acts as a master repressor of EE cell specification in Drosophila ISC lineages primarily by suppressing AS-C genes.
