期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28369-7
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资金
- European Union [INTENS 668294, STEMHEALTH ERCCoG682665]
- Novo Nordisk Foundation [NNF17OC0028730, NNF18OC0034066, NNF20OC0064376, NNF17CC0027852, NNF21CC0073729]
- Danish Cancer Society [R124-A7724]
- Marie Curie fellowship programme [656099/H2020-MSCA-IF-2014]
- EMBO Long-Term fellowship [ALTE 946-2019]
- Howard Hughes Medical Institute (HHMI)
- Mathers Foundation
- Ludwig Foundation
- NIH [1R01DK115728-01A1]
- Novo Nordisk Foundation Center for Stem Cell Biology
The gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog, which is crucial for the formation and regionalization of the small intestine.
The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine. Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI.
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