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Molecular and Cellular Biology, September 2005, p. 7868-7878, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7868-7878.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

c-Myc Is Required for the Formation of Intestinal Crypts but Dispensable for Homeostasis of the Adult Intestinal Epithelium

Michael D. Bettess,1 Nicole Dubois,1 Mark J. Murphy,1 Christelle Dubey,1 Catherine Roger,1 Sylvie Robine,2 and Andreas Trumpp1*

Genetics and Stem Cell Laboratory, Swiss Institute for Experimental Cancer Research, and Swiss Institute of Technology Lausanne, 1066 Epalinges, Switzerland,1 UMR 144 CNRS, Institut Curie, 75248 Paris Cedex 05, France2

Received 21 December 2004/ Returned for modification 5 April 2005/ Accepted 29 May 2005

In self-renewing tissues such as the skin epidermis and the bone marrow, Myc proteins control differentiation of stem cells and proliferation of progenitor cell types. In the epithelium of the small intestine, we show that c-Myc and N-Myc are expressed in a differential manner. Whereas c-Myc is expressed in the proliferating transient-amplifying compartment of the crypts, N-Myc is restricted to the differentiated villus epithelium and a single cell located near the crypt base. c-Myc has been implicated as a critical target of the canonical Wnt pathway, which is essential for formation and maintenance of the intestinal mucosa. To genetically assess the role of c-Myc during development and homeostasis of the mammalian intestine we induced deletion of the c-mycflox allele in the villi and intestinal stem cell-bearing crypts of juvenile and adult mice, via tamoxifen-induced activation of the CreERT2 recombinase, driven by the villin promoter. Absence of c-Myc activity in the juvenile mucosa at the onset of crypt morphogenesis leads to a failure to form normal numbers of crypts in the small intestine. However, all mice recover from this insult to form and maintain a normal epithelium in the absence of c-Myc activity and without apparent compensation by N-Myc or L-Myc. This study provides genetic and molecular evidence that proliferation and expansion of progenitors necessary to maintain the adult intestinal epithelium can unexpectedly occur in a Myc-independent manner.

* Corresponding author. Mailing address: Genetics and Stem Cell Laboratory, Swiss Institute for Experimental Cancer Research, and Swiss Institute of Technology Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41 21 692 5817. Fax: 41 21 652 6933. E-mail: Andreas.Trumpp{at}isrec.ch.

Molecular and Cellular Biology, September 2005, p. 7868-7878, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7868-7878.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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