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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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. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0078519</identifier><identifier>PMID: 24205248</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e78519-e78519</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Tan et al 2013 Tan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e71e64e7a61b3e70ad4e2c0319c92d73d4632b18d19a7b630c45fb45ae4bde03</citedby><cites>FETCH-LOGICAL-c692t-e71e64e7a61b3e70ad4e2c0319c92d73d4632b18d19a7b630c45fb45ae4bde03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804607/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804607/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24205248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Vinciguerra, Manlio</contributor><creatorcontrib>Tan, Chin Wee</creatorcontrib><creatorcontrib>Hirokawa, Yumiko</creatorcontrib><creatorcontrib>Gardiner, Bruce S</creatorcontrib><creatorcontrib>Smith, David W</creatorcontrib><creatorcontrib>Burgess, Antony W</creatorcontrib><title>Colon cryptogenesis: asymmetric budding</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Aberration</subject><subject>Adenomatous polyposis coli</subject><subject>Adenomatous polyposis coli protein</subject><subject>Animals</subject><subject>Asymmetry</subject><subject>beta Catenin - metabolism</subject><subject>Biology</subject><subject>Budding</subject><subject>Cadherins - metabolism</subject><subject>Cancer</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Colon</subject><subject>Colon - metabolism</subject><subject>Colon - pathology</subject><subject>Colon - physiology</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Crypts</subject><subject>E-cadherin</subject><subject>Heterogeneity</subject><subject>Image analysis</subject><subject>Image processing</subject><subject>Immunofluorescence</subject><subject>Intestinal Mucosa - 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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. 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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