Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors

Silvia Maretto, Michelangelo Cordenonsi, Sirio Dupont, Paola Braghetta, Vania Broccoli, A. Bassim Hassan, Dino Volpin, Giorgio M. Bressan, Stefano Piccolo

Research output: Contribution to journalArticlepeer-review

Abstract

Wnt/β-catenin signaling plays key roles in several developmental and pathological processes. Domains of Wnt expression have been extensively investigated in the mouse, but the tissues receiving the signal remain largely unidentified. To define which cells respond to activated β-catenin during mammalian development, we generated the β-catenin-activated transgene driving expression of nuclear β-galactosidase reporter (BAT-gal) transgenic mice, expressing the lacZ gene under the control of β-catenin/T cell factor responsive elements. Reporter gene activity is found in known organizing centers, such as the midhindbrain border and the limb apical ectodermal ridge. Moreover, BAT-gal expression identifies novel sites of Wnt signaling, like notochord, endothelia, and areas of the adult brain, revealing an unsuspected dynamic pattern of β-catenin transcriptional activity. Expression of the transgene was analyzed in mutant backgrounds. In lipoprotein receptor-related protein 6-null homozygous mice, which lack a Wnt coreceptor, BAT-gal staining is absent in mutant tissues, indicating that BAT-gal mice are bona fide in vivo indicators of Wnt/β-catenin signaling. Analyses of BAT-gal expression in the adenomatous polyposis coli (multiple intestinal neoplasia/+) background revealed β- catenin transcriptional activity in intestinal adenomas but surprisingly not in normal crypt cells. In summary, BAT-gal mice unveil the entire complexity of Wnt/β-catenin signaling in mammals and have broad application potentials for the identification of Wnt-responsive cell populations in development and disease.

Original languageEnglish
Pages (from-to)3299-3304
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
Publication statusPublished - Mar 18 2003

Keywords

  • Adenomatous polyposis coli
  • Colon cancer
  • Lipoprotein receptor-related protein 6
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics
  • General

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