Colon cryptogenesis: asymmetric budding

The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency...

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Veröffentlicht in:PloS one 2013-10, Vol.8 (10), p.e78519-e78519
Hauptverfasser: Tan, Chin Wee, Hirokawa, Yumiko, Gardiner, Bruce S, Smith, David W, Burgess, Antony W
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container_end_page e78519
container_issue 10
container_start_page e78519
container_title PloS one
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creator Tan, Chin Wee
Hirokawa, Yumiko
Gardiner, Bruce S
Smith, David W
Burgess, Antony W
description The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers.
doi_str_mv 10.1371/journal.pone.0078519
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A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. 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The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24205248</pmid><doi>10.1371/journal.pone.0078519</doi><tpages>e78519</tpages><oa>free_for_read</oa></addata></record>
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subjects Aberration
Adenomatous polyposis coli
Adenomatous polyposis coli protein
Animals
Asymmetry
beta Catenin - metabolism
Biology
Budding
Cadherins - metabolism
Cancer
Cell adhesion
Cell adhesion & migration
Colon
Colon - metabolism
Colon - pathology
Colon - physiology
Colon cancer
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Colorectal cancer
Crypts
E-cadherin
Heterogeneity
Image analysis
Image processing
Immunofluorescence
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Intestinal Mucosa - physiology
Medical research
Mice
Mice, Inbred C57BL
Microscopy
Mucosa
Polyposis coli
Rodents
Signal Transduction - physiology
Signaling
Small intestine
Wnt protein
Wnt Signaling Pathway - physiology
β-Catenin
title Colon cryptogenesis: asymmetric budding
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