Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling

Martti Maimets, Marianne Terndrup Pedersen, Jordi Guiu, Jes Dreier, Malte Thodberg, Yasuko Antoku, Pawel J. Schweiger, Leonor Rib, Raul Bardini Bressan, Yi Miao, K. Christopher Garcia, Albin Sandelin, Palle Serup and Kim B. Jensen ()
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Martti Maimets: University of Copenhagen
Marianne Terndrup Pedersen: University of Copenhagen
Jordi Guiu: University of Copenhagen
Jes Dreier: University of Copenhagen
Malte Thodberg: University of Copenhagen
Yasuko Antoku: University of Copenhagen
Pawel J. Schweiger: University of Copenhagen
Leonor Rib: University of Copenhagen
Raul Bardini Bressan: University of Copenhagen
Yi Miao: Stanford University School of Medicine
K. Christopher Garcia: Stanford University School of Medicine
Albin Sandelin: University of Copenhagen
Palle Serup: University of Copenhagen
Kim B. Jensen: University of Copenhagen

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28369-7

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