Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Kruppel-like factor 9.
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.
Simmen
Frank A
FA
Arkansas Children's Nutrition Center, 1120 Marshall St., Little Rock, AR 72202, USA. simmenfranka@uams.edu
Xiao
Rijin
R
Velarde
Michael C
MC
Nicholson
Rachel D
RD
Bowman
Margaret T
MT
Fujii-Kuriyama
Yoshiaki
Y
Oh
S Paul
SP
Simmen
Rosalia C M
RC
D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D020397:Goblet Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D019879:Paneth Cells / Q000378:metabolism; D019899:Paracrine Communication / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014158:Transcription, Genetic
C489675:Klf9 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger