title: Mesenchymal expression of Foxl1, a winged helix transcriptional factor, regulates generation and maintenance of gut-associated lymphoid organs.
abstract: The Foxl1 gene, which encodes a winged helix transcriptional regulator, is expressed in the mesenchymal layer of developing and mature gastrointestinal tract. Foxl1-deficient mice exhibit various defects not only in the epithelial layer of the gastrointestinal tract but also in gut-associated lymphoid tissues. In the small intestine of Foxl1-deficient mice, the formation of Peyer's patches is affected, particularly in the caudal region. This alteration is shown to be due to the delayed formation of Peyer's patches organizing centers as revealed by the expressions of VCAM1 and IL-7 receptor alpha-chain at 17.5 days postcoitus. Peyer's patch defects are concordant with the significantly decreased expression of Lymphotoxin beta-receptor in the caudal region of fetal intestine. Foxl1 is suggested to regulate the responsiveness of fetal intestinal mesenchymal cells to inductive signals mediated by Lymphotoxins during Peyer's patch organogenesis. In addition, constitutive outgrowth of colonic patches due to defects in radioresistant stromal components of colonic patches are seen in Foxl1-deficient mice. Because of the functional similarities of hypertrophic colonic patches to those seen in hapten-induced experimental colitis, this hypertrophy is suggested to involve Lymphotoxin beta-receptor signaling. Together, the data suggest that Foxl1 might be involved in cellular responses of gut-associated lymphoid tissues dependent upon the Lymphotoxins/Lymphotoxin beta-receptor axis.
authors.affiliation: Department of Molecular Embryology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Fukuda
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toru
authors.initials: T
authors.lastname: Sato
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Furumoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizutani-Koseki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
authors.forename: Motoko
authors.initials: M
authors.lastname: Kimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D004064:Digestive System / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D008221:Lymphoid Tissue / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D053259:Lymphotoxin beta Receptor; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D020395:Receptors, Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; C415350:interleukin-7 receptor, alpha chain