Dpp Signaling Determines Regional Stem Cell Identity in the Regenerating Adult Drosophila Gastrointestinal Tract

Abstract

Summary The gastrointestinal tract is lined by a series of epithelia that share functional requirements, but also have distinct, highly specialized roles. Distinct populations of somatic stem cells (SCs) regenerate these epithelia, yet the mechanisms that maintain regional identities of these SCs are not well understood. Here, we identify a role for the BMP-like Dpp signaling pathway in diversifying regenerative processes in the adult gastrointestinal tract of Drosophila. Dpp secreted from enterocytes at the boundary between the posterior midgut (PM) and the middle midgut (MM) sets up a morphogen gradient that selectively directs copper cell (CC) regeneration from gastric SCs in the MM and thus determines the size of the CC region. In vertebrates, deregulation of BMP signaling has been associated with Barrett’s metaplasia, where the squamous esophageal epithelium is replaced by a columnar epithelium, suggesting that the maintenance of regional SC identities by BMP is conserved.

EGFR and Notch signaling respectively regulate proliferative activity and multiple cell lineage differentiation of Drosophila gastric stem cells

“…Recent studies have revealed an important role for Decapentaplegic (Dpp) signaling in the differentiation of CCs in adult Drosophila [22,23]. GSSCs that are mutant for Dpp signaling components, such as the receptor Thickvein (Tkv) or the downstream transcriptional factor Mothers against Dpp (Mad), can no longer effectively produce CCs [22,23].…”

“…GSSCs that are mutant for Dpp signaling components, such as the receptor Thickvein (Tkv) or the downstream transcriptional factor Mothers against Dpp (Mad), can no longer effectively produce CCs [22,23]. To understand the epistatic relationships between Notch and Dpp signaling in CC differentiation, we asked whether forced expression of N icd could induce differentiation of tkv or mad mutant progenitor cells.…”

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

“…The midgut extends from the cardia until the junction with the hindgut, where the Malpighian tubules connect with the gut ( Figure 1B). Detailed histological and molecular analysis demonstrates a complex degree of compartmentalization in the adult fly midgut (Buchon et al, 2013b) (Marianes and Spradling, 2013) (Li et al, 2013a). Further details on gut compartmentalization, the perithropic membrane and Malpighian tubules can be found in different articles of this issue.…”

Specification of regional intestinal stem cell identity during Drosophila metamorphosis

“…Recently, we and others have shown that BMP signaling is necessary for the formation of new copper cells by ISCs located in the middle midgut (Guo et al, 2013;Li et al, 2013). Additionally, injury-induced BMP signaling acts autonomously in ISCs in the anterior and posterior midgut to limit their proliferative response to enterocyte damage (Guo et al, 2013).…”

“…The genes encoding the secreted ligands Decapentaplegic (Dpp) and Wingless (Wg) are expressed at the junction of these parasegments and lead to the expression of labial in a subset of midgut epithelial cells (Bilder et al, 1998;Hoppler and Bienz, 1995;Immerglück et al, 1990;Mann and Abu-Shaar, 1996). In the adult midgut, BMP (Guo et al, 2013;Li et al, 2013) and Wnt (Strand and Micchelli, 2011) signals are necessary for labial expression and copper cell formation. Yet members of both the BMP (Guo et al, 2013) and Wnt (Lin et al, 2008) signaling pathways are widely expressed.…”