Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates

被引：100

作者：

Mattes, Benjamin ^{[1
,2
]}

Dang, Yonglong ^{[2
,13
]}

Greicius, Gediminas ^{[3
]}

Kaufmann, Lilian Tamara ^{[4
]}

Prunsche, Benedikt ^{[5
]}

Rosenbauer, Jakob ^{[6
]}

Stegmaier, Johannes ^{[7
,8
]}

Mikut, Ralf ^{[7
]}

Oezbek, Suat ^{[9
]}

Nienhaus, Gerd Ulrich ^{[2
,5
,10
,11
]}

Schug, Alexander ^{[6
,12
]}

Virshup, David M. ^{[3
]}

Scholpp, Steffen ^{[1
,2
]}

机构：

[1] Univ Exeter, Living Syst Inst, Sch Biosci, Coll Life & Environm Sci, Exeter, Devon, England

[2] Karlsruhe Inst Technol, Inst Toxicol & Genet, Karlsruhe, Germany

[3] Duke NUS Med Sch, Program Canc & Stem Cell Biol, Singapore, Singapore

[4] Univ Hosp Heidelberg, Inst Human Genet, Heidelberg, Germany

[5] Karlsruhe Inst Technol, Inst Appl Phys, Karlsruhe, Germany

[6] Julich Supercomp Ctr, John von Neumann Inst Comp, Julich, Germany

[7] Karlsruhe Inst Technol, Inst Automat & Appl Informat, Karlsruhe, Germany

[8] Rhein Westfal TH Aachen, Inst Imaging & Comp Vis, Aachen, Germany

[9] Heidelberg Univ, Ctr Organismal Studies, Karlsruhe, Germany

[10] Karlsruhe Inst Technol, Inst Nanotechnol, Karlsruhe, Germany

[11] Univ Illinois, Dept Phys, Urbana, IL USA

[12] Karlsruhe Inst Technol, Steinbuch Ctr Comp, Karlsruhe, Germany

[13] German Canc Res Ctr, Dept Mol Neurosci, Heidelberg, Germany

来源：

ELIFE | 2018年 / 7卷

基金：

英国生物技术与生命科学研究理事会;

关键词：

RECEPTOR TYROSINE KINASE; INTESTINAL STEM-CELLS; WNT PROTEINS; ROR2; PATHWAY; EXPRESSION; ZEBRAFISH; SECRETION; ACTIVATION; TRANSPORT;

D O I：

10.7554/eLife.36953

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Signaling filopodia, termed cytonemes, are dynamic actin-based membrane structures that regulate the exchange of signaling molecules and their receptors within tissues. However, how cytoneme formation is regulated remains unclear. Here, we show that Wnt/planar cell polarity (PCP) autocrine signaling controls the emergence of cytonemes, and that cytonemes subsequently control paracrine Wnt/beta-catenin signal activation. Upon binding of the Wnt family member Wnt8a, the receptor tyrosine kinase Ror2 becomes activated. Ror2/PCP signaling leads to the induction of cytonemes, which mediate the transport of Wnt8a to neighboring cells. In the Wnt-receiving cells, Wnt8a on cytonemes triggers Wnt/beta-catenin-dependent gene transcription and proliferation. We show that cytoneme-based Wnt transport operates in diverse processes, including zebrafish development, murine intestinal crypt and human cancer organoids, demonstrating that Wnt transport by cytonemes and its control via the Ror2 pathway is highly conserved in vertebrates.

引用

页数：28

共 97 条

[21] Visualization of a short-range Wnt gradient in the intestinal stem-cell niche [J].