Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling.
Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling.
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DOI：
10.1038/s41467-022-28369-7
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发表时间：
2022-02-07
影响因子：
16.6
通讯作者：
Jensen KB
中科院分区：
文献类型：
--
作者：
Maimets M;Pedersen MT;Guiu J;Dreier J;Thodberg M;Antoku Y;Schweiger PJ;Rib L;Bressan RB;Miao Y;Garcia KC;Sandelin A;Serup P;Jensen KB
器官在解剖上被划分成不同的部分，以满足特定的功能。在小肠(SI)中，区域化使食物和营养吸收的顺序处理成为可能。虽然一些研究表明非上皮细胞在发育和动态平衡过程中的关键重要性，但这些细胞在形态发生过程中对区域化的贡献程度仍未被探索。在这里，我们发现了一种间充质-上皮间充质-上皮性串扰，它在形态发生后期塑造了发育中的SI。我们发现，在体外，上皮下间充质细胞的特征是支持Wnt信号和刺激上皮生长的因子的梯度。这种梯度影响上皮基因的表达和沿SI前后轴的区域绒毛形成。值得注意的是，我们进一步提供了Wnt信号直接调节Sonic Hedgehog(SHH)上皮表达的证据，Sonic Hedgehog(SHH)反过来作用于间充质细胞来驱动绒毛的形成。综上所述，我们的结果揭示了Wnt和Hedgehog信号在不同细胞间隔之间的机械联系，这对于前后部区域化和SI的正确形成是至关重要的。小肠是通过上皮细胞和间充质细胞之间的串扰形成的。在这里，作者表明，Wnt信号沿前后轴的梯度调节Sonic Hedgehog，这是正确形成和定位小肠所必需的。
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. 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.
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影响因子：
11.8
作者：
Elmentaite R;Ross ADB;Roberts K;James KR;Ortmann D;Gomes T;Nayak K;Tuck L;Pritchard S;Bayraktar OA;Heuschkel R;Vallier L;Teichmann SA;Zilbauer M
通讯作者：
Zilbauer M
影响因子：
16.2
作者：
Cho C;Smallwood PM;Nathans J
通讯作者：
Nathans J
肠上皮中β1整联蛋白的条件缺失会导致刺猬表达，肠道增生和早期产后致死性的丧失。
影响因子：
7.8
作者：
Jones, Robert G.;Li, Xiufen;Gray, Phillip D.;Kuang, Jinqiu;Clayton, Frederic;Samowitz, Wade S.;Madison, Blair B.;Gumucio, Deborah L.;Kuwada, Scott K.
通讯作者：
Kuwada, Scott K.
DOI：
10.1242/dev.163014
发表时间：
2018-05-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chung MI;Bujnis M;Barkauskas CE;Kobayashi Y;Hogan BLM
通讯作者：
Hogan BLM
影响因子：
12.3
作者：
Frietze S;Wang R;Yao L;Tak YG;Ye Z;Gaddis M;Witt H;Farnham PJ;Jin VX
通讯作者：
Jin VX