<i>Drosophila</i> and mouse intestinal stem cells are spatiotemporally specified by Notch suppression and Wnt activation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41337595.
- Also identified by DOI 10.1126/sciadv.ady7272 and PMC identifier 12674121.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The specification of intestinal stem cells (ISCs) during development is critical for maintaining intestinal homeostasis. However, the mechanisms underlying this process remain elusive. Here, by counting and tracing ISC in <i>Drosophila</i> pupal midgut, we show that ISCs are specified within a narrow 12-hour developmental window, with ~150 ISCs emerging from a pool of ~6000 intestinal epithelial cells. Single-cell sequencing revealed the involvement of Notch and Wnt signaling, with genetic experiments demonstrating that ISC specification requires both Notch suppression and Wnt activation. Furthermore, we showed that Wnt signaling is activated in discrete spatial domains, and Notch-mediated lateral inhibition specifies ISCs in these Wnt-active zones, achieving a ratio of ~1/40. Notably, Notch suppression also promoted the specification of Lgr5<sup>+</sup> progenitors in the mouse embryonic intestine. Together, our data show that Wnt activation defines niches permissive for ISC fate, whereas Notch suppression licenses fate commitment, a spatiotemporal coordination conserved from insects to mammals.
Medical subject headings
- Receptors, Notch
- Stem Cells
- Drosophila Proteins
- Intestines
- Wnt Signaling Pathway
- Wnt Proteins