Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract

Mech Dev. 2002 May;113(2):121-30. doi: 10.1016/s0925-4773(02)00032-1.


Recent studies have shown that aberrantly expressed gastrin-releasing peptide (GRP) and its receptor (GRP-R) critically regulate tumor cell differentiation in colon cancers developing in humans and mice. This finding suggested that the ability of GRP/GRP-R to promote a well-differentiated phenotype in colon cancer might reflect a re-capitulation of a normal role in regulating intestinal organogenesis. To determine if this was the case, we compared and contrasted intestinal development in GRPR-/- mice with their wild type littermates. GRP/GRP-R co-expression in wild type mice was only observed in villous enterocytes between N-1 and N-12. During this time frame villous growth was completely attenuated in GRPR-/- mice. The contribution of GRP/GRP-R to villous growth was due to their act in increasing enterocyte proliferation prior to N-8 but increasing enterocyte size thereafter. From N-12 onwards, small intestinal villous growth in GRPR-/- mice resumed such that no difference in this structure could be detected at adulthood between mice of either genotype. We next studied GRP/GRP-R expression in human abortuses. These proteins were co-expressed by villous enterocytes only between weeks 14 and 20 post-conception, a time frame analogous to when they are expressed in the murine intestine. Thus, this study shows for the first time that GRP/GRP-R play a transient and non-critical role in intestinal development, yet provides a rationale for their re-appearance in colon cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aborted Fetus
  • Animals
  • Cell Division
  • Cell Separation
  • Digestive System / embryology*
  • Enterocytes / metabolism*
  • Flow Cytometry
  • Gastrin-Releasing Peptide / biosynthesis
  • Gastrin-Releasing Peptide / physiology*
  • Genotype
  • Humans
  • Immunohistochemistry
  • Mice
  • Phenotype
  • Receptors, Bombesin / biosynthesis
  • Receptors, Bombesin / physiology*
  • Time Factors


  • Receptors, Bombesin
  • Gastrin-Releasing Peptide