Analysis of Wnt signalling dynamics during colon crypt development in 3D culture
Journal Title
Scientific Reports
Publication Type
Journal Article
Abstract
Many systems biology studies lack context-relevant data and as a consequence the predictive capabilities can be limited in developing targeted cancer therapeutics. Production of colon crypt in vitro is ideal for studying colon systems biology. This report presents the first production of, to our knowledge, physiologically-shaped, functional colon crypts in vitro (i.e. single crypts with cells expressing Mucin 2 and Chromogranin A). Time-lapsed monitoring of crypt formation revealed an increased frequency of single-crypt formation in the absence of noggin. Using quantitative 3D immunofluorescence of β-catenin and E-cadherin, spatial-temporal dynamics of these proteins in normal colon crypt cells stimulated with Wnt3A or inhibited by cycloheximide has been measured. Colon adenoma cultures established from APCmin/+ mouse have developmental differences and β-catenin spatial localization compared to normal crypts. Quantitative data describing the effects of signalling pathways and proteins dynamics for both normal and adenomatous colon crypts is now within reach to inform a systems approach to colon crypt biology.
Publisher
Nature Publishing Group
WEHI Research Division(s)
Structural Biology
PubMed ID
26087250
Publisher's Version
https://doi.org/10.1038/srep11036
Open Access at Publisher's Site
http://www.nature.com/articles/srep11036
NHMRC Grants
NHMRC/1029628 NHMRC/487922
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-10-28 03:35:35
Last Modified: 2015-10-28 03:59:53
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