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Am J Physiol Gastrointest Liver Physiol 292: G1757-G1769, 2007. First published March 22, 2007; doi:10.1152/ajpgi.00013.2007
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MUCOSAL BIOLOGY

Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Krüppel-like factor 9

Frank A. Simmen,1,2 Rijin Xiao,1,2 Michael C. Velarde,1,2 Rachel D. Nicholson,2 Margaret T. Bowman,2 Yoshiaki Fujii-Kuriyama,3 S. Paul Oh,4 and Rosalia C. M. Simmen1,2

Department of 1Physiology and Biophysics and 2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas; 3TARA Center, University of Tsukuba, 1-1-1 Tennodai Tsukuba 305-8577, Japan; and 4Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida

Submitted 6 January 2007 ; accepted in final form 14 March 2007

Krüppel-like factor 9 (Klf9), a zinc-finger transcription factor, is implicated in the control of cell proliferation, cell differentiation, and cell fate. Using Klf9-null mutant mice, we have investigated the involvement of Klf9 in intestine crypt-villus cell renewal and lineage determination. We report the predominant expression of Klf9 gene in small and large intestine smooth muscle (muscularis externa). Jejunums null for Klf9 have shorter villi, reduced crypt stem/transit cell proliferation, and altered lineage determination as indicated by decreased and increased numbers of goblet and Paneth cells, respectively. A stimulatory role for Klf9 in villus cell migration was demonstrated by bromodeoxyuridine labeling. Results suggest that Klf9 controls the elaboration, from intestine smooth muscle, of molecular mediator(s) of crypt cell proliferation and lineage determination and of villus cell migration.

Krüppel-like; Igfbp4; Ptk6; stem cells; colon; smooth muscle


Address for reprint requests and other correspondence: F. A. Simmen, Arkansas Children's Nutrition Center, 1120 Marshall St., Little Rock, AR 72202 (e-mail: simmenfranka{at}uams.edu)






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