Transcriptional control of stem cell maintenance in theDrosophilaintestine

Abstract

SUMMARYAdult stem cells maintain tissue homeostasis by controlling the proper balance of stem cell self-renewal and differentiation. The adult midgut of Drosophila contains multipotent intestinal stem cells (ISCs) that self-renew and produce differentiated progeny. Control of ISC identity and maintenance is poorly understood. Here we find that transcriptional repression of Notch target genes by a Hairless-Suppressor of Hairless complex is required for ISC maintenance, and identify genes of the Enhancer of split complex [E(spl)-C] as the major targets of this repression. In addition, we find that the bHLH transcription factor Daughterless is essential to maintain ISC identity and that bHLH binding sites promote ISC-specific enhancer activity. We propose that Daughterless-dependent bHLH activity is important for the ISC fate and that E(spl)-C factors inhibit this activity to promote differentiation.

Sending the right signal: Notch and stem cells

“…The HES/HEY genes are not, however, the only targets of Notch signaling as in many tissues loss of HES/HEY genes does not recapitulate all of the phenotypes of loss of Notch activity indicating the existence of addition target genes [54][55][56][57][58]. Indeed, there are a large number of cellspecific Notch targets [59,60].…”

“…In addition, Notch target genes are also controlled through transcriptional repression [54]. Loss of the co-repressor Hairless in the ISC results in loss of ISCs, at least in part by its terminal differentiation, suggesting that Hairless acts in combination with Su(H)/RBP-Jk to keep the expression of Notch target genes repressed in the ISC [54].…”

“…Loss of the co-repressor Hairless in the ISC results in loss of ISCs, at least in part by its terminal differentiation, suggesting that Hairless acts in combination with Su(H)/RBP-Jk to keep the expression of Notch target genes repressed in the ISC [54]. There is also evidence that chromatin modifications are also required to maintain Notch target genes in a repressed state in the ISC, as loss of a ubiquitin protease that deubiquitylates histone H2B results in terminal differentiation of the ISC [156].…”

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster

“…The larval midgut is an endothelial tube containing two differentiated cell types, namely, enterocytes and enteroendocrine cells, which arise from stem cell crypts located within the gut and differentiate into either cell type in a Notch signaling pathway-dependant manner [18,19]. Depending on position cues within the gut tube, the enterocytes develop a wide variety of morphologies and functions and represent the majority of the cells within the midgut.…”

Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes

“…Functionally, FOXD3 has been implicated in the control of differentiation in multiple systems, mostly preventing appropriate maturation [40,[112][113][114][115]. Interestingly, accumulated data suggest that this mode of action, through cell fate restriction, is a central hallmark of stem cells in general [116][117][118][119]. As such, it has been shown that ectopic expression of FOXD3 in the neural tube promotes a NC-like phenotype and continued expression of FOXD3 in migrating NCCs interferes with their subsequent differentiation in NC derivatives [112,113], suggesting that FOXD3 may play a critical role in establishing or maintaining proliferating and self-renewing progenitor cell populations.…”