@article{Perea:2017:10.15252/embj.201696247,
author = {Perea, D and Guiu, J and Hudry, B and Konstantinidou, C and Milona, A and Hadjieconomou, D and Carroll, T and Hoyer, N and Natarajan, D and Kallijärvi, J and Walker, JA and Soba, P and Thapar, N and Burns, AJ and Jensen, KB and Miguel-Aliaga, I},
doi = {10.15252/embj.201696247},
journal = {EMBO Journal},
pages = {3029--3045},
title = {Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.},
url = {http://dx.doi.org/10.15252/embj.201696247},
volume = {36},
year = {2017}
}

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TY  - JOUR
AB  - Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homoeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.
AU  - Perea,D
AU  - Guiu,J
AU  - Hudry,B
AU  - Konstantinidou,C
AU  - Milona,A
AU  - Hadjieconomou,D
AU  - Carroll,T
AU  - Hoyer,N
AU  - Natarajan,D
AU  - Kallijärvi,J
AU  - Walker,JA
AU  - Soba,P
AU  - Thapar,N
AU  - Burns,AJ
AU  - Jensen,KB
AU  - Miguel-Aliaga,I
DO  - 10.15252/embj.201696247
EP  - 3045
PY  - 2017///
SN  - 0261-4189
SP  - 3029
TI  - Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.
T2  - EMBO Journal
UR  - http://dx.doi.org/10.15252/embj.201696247
UR  - http://hdl.handle.net/10044/1/51967
VL  - 36
ER  - 

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