The fibroblast growth factor pathway serves a regulatory role in proliferation and apoptosis in the pathogenesis of intestinal atresia

Timothy J. Fairbanks, Frederic G. Sala, Robert Kanard, Jennifer L. Curtis, Pierre M. Del Moral, Stijn De Langhe, David Warburton, Kathryn D. Anderson, Saverio Bellusci, R. Cartland Burns, Allan Goldstein, Jean Martin Laberge, Kerry Bergman, Edmund Yang, Patricia Donahoe, Marshall Schwartz

Abstract

Background/Purpose: Intestinal atresia occurs in 1:5000 live births and is a neonatal challenge. Fibroblast growth factor receptor 2b (Fgfr2b) is a critical developmental regulator of proliferation and apoptosis in multiple organ systems including the gastrointestinal tract (GIT). Fgfr2b invalidation results in an autosomal recessive intestinal atresia phenotype. This study evaluates the role of Fgfr2b signaling in regulating proliferation and apoptosis in the pathogenesis of intestinal atresia. Methods: Wild-type and Fgfr2b -/- embryos were harvested from timed pregnant mice. The GIT was harvested using standard techniques. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) was used to evaluate apoptosis and bromodeoxyuridine to assess proliferation by standard protocols. Photomicrographs were compared (Institutional Animal Care and Use Committee-approved protocol 32-02). Results: Wild-type and mutant GIT demonstrate that deletion of the Fgfr2b gene results in inhibition of epithelial proliferation and increased apoptosis. Inhibited proliferation and increased apoptosis are specific to those tissues of normal Fgfr2b expression, corresponding to the site of intestinal atresia. Conclusions: The absence of embryonic GIT Fgfr2b expression results in decreased proliferation and increased apoptosis resulting in GIT atresia. The regulation of proliferation and apoptosis in intestinal cells as a genetically based cause of intestinal atresia represents a novel consideration in the pathogenesis of intestinal atresia.

Original languageEnglish (US)
Pages (from-to)132-136
Number of pages5
JournalJournal of pediatric surgery
Volume41
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Apoptosis
  • FGFR2B
  • Fibroblast growth factor
  • Intestinal atresia
  • Proliferation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

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