Colon cryptogenesis: asymmetric budding

PLoS One. 2013 Oct 21;8(10):e78519. doi: 10.1371/journal.pone.0078519. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Colon / metabolism
  • Colon / pathology*
  • Colon / physiology*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / physiology
  • Wnt Signaling Pathway / physiology
  • beta Catenin / metabolism

Substances

  • Cadherins
  • beta Catenin

Grant support

This work is supported by National Health and Medical Research Council (NHMRC) Project Grant GNT1029628, Program Grant 487922 and by funds from the Operational Infrastructure Support Program provided by the Victorian Government, Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Additionally the manuscript is solely the responsibility of the institutions and individual authors and does not reflect the views of NHMRC.