Submitted on January 6, 2007
Accepted on March 14, 2007
Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Krüppel-like factor 9 (Klf9)
Frank A. Simmen1*, Rijin Xiao1, Michael C. Velarde2, Rachel D. Nicholson2, Margaret T. Bowman1, Yoshiaki Fujii-Kuriyama3, S. Paul Oh4, and Rosalia C.M. Simmen1
1 Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
2 Physiology and Biophysics, University of Arkansas for Medical Sci, Little Rock, Arkansas, United States
3 TARA Center, University of Tsukuba, Tsukuba, Japan
4 Physiology and Functional Genomics, University of Florida, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: simmenfranka{at}uams.edu.
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 BrdU 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.
