Imperial College London

Dr Charlotte Dean

Faculty of MedicineNational Heart & Lung Institute

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3174c.dean

 
 
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Location

 

360Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rao-Bhatia:2020:10.1016/j.devcel.2020.02.003,
author = {Rao-Bhatia, A and Zhu, M and Yin, W-C and Coquenlorge, S and Zhang, X and Woo, J and Sun, Y and Dean, CH and Liu, A and Hui, C-C and Shivdasani, RA and McNeill, H and Hopyan, S and Kim, T-H},
doi = {10.1016/j.devcel.2020.02.003},
journal = {Developmental Cell},
pages = {647--658.e6},
title = {Hedgehog-activated fat4 and PCP pathways mediate mesenchymal cell clustering and villus formation in gut development},
url = {http://dx.doi.org/10.1016/j.devcel.2020.02.003},
volume = {52},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - During development, intestinal epithelia undergo dramatic morphogenesis mediated by mesenchymal signaling to form villi, which are required for efficient nutrient absorption and host defense. Although both smooth-muscle-induced physical forces and mesenchymal cell clustering beneath emerging villi are implicated in epithelial folding, the underlying cellular mechanisms are unclear. Hedgehog (Hh) signaling can mediate both processes. We therefore analyzed its direct targetome and revealed GLI2 transcriptional activation of atypical cadherin and planar cell polarity (PCP) genes. By examining Fat4 and Dchs1 knockout mice, we demonstrate their critical roles in villus formation. Analyses of PCP-mutant mice and genetic interaction studies show that the Fat4-Dchs1 axis acts in parallel to the core-Vangl2 PCP axis to control mesenchymal cell clustering. Moreover, live light-sheet fluorescence microscopy and cultured PDGFRα+ cells reveal a requirement for PCP in their oriented cell migration guided by WNT5A. Therefore, mesenchymal PCP induced by Hh signaling drives cell clustering and subsequent epithelial remodeling.
AU - Rao-Bhatia,A
AU - Zhu,M
AU - Yin,W-C
AU - Coquenlorge,S
AU - Zhang,X
AU - Woo,J
AU - Sun,Y
AU - Dean,CH
AU - Liu,A
AU - Hui,C-C
AU - Shivdasani,RA
AU - McNeill,H
AU - Hopyan,S
AU - Kim,T-H
DO - 10.1016/j.devcel.2020.02.003
EP - 658
PY - 2020///
SN - 1534-5807
SP - 647
TI - Hedgehog-activated fat4 and PCP pathways mediate mesenchymal cell clustering and villus formation in gut development
T2 - Developmental Cell
UR - http://dx.doi.org/10.1016/j.devcel.2020.02.003
UR - https://www.sciencedirect.com/science/article/pii/S153458072030099X?via%3Dihub
VL - 52
ER -