Fukuda Katsuyuki, Yoshida Hisahiro, Sato Toru, Furumoto Taka-aki, Mizutani-Koseki Yoko, Suzuki Yasuo, Saito Yasushi, Takemori Toshitada, Kimura Motoko, Sato Hiroshi, Taniguchi Masaru, Nishikawa Shin-ichi, Nakayama Toshinori, Koseki Haruhiko
Department of Molecular Embryology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Dev Biol. 2003 Mar 15;255(2):278-89. doi: 10.1016/s0012-1606(02)00088-x.
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.
Foxl1基因编码一种翼状螺旋转录调节因子，在发育中和成熟的胃肠道间充质层中表达。Foxl1基因缺陷的小鼠不仅在胃肠道上皮层表现出各种缺陷，在肠道相关淋巴组织中也存在缺陷。在Foxl1基因缺陷小鼠的小肠中，派尔集合淋巴结的形成受到影响，尤其是在尾部区域。这种改变被证明是由于交配后17.5天时VCAM1和IL - 7受体α链的表达所揭示的派尔集合淋巴结组织中心形成延迟所致。派尔集合淋巴结缺陷与胎儿肠道尾部区域淋巴毒素β受体表达显著降低一致。在派尔集合淋巴结器官发生过程中，Foxl1被认为可调节胎儿肠道间充质细胞对淋巴毒素介导的诱导信号的反应性。此外，在Foxl1基因缺陷小鼠中可见由于结肠派尔集合淋巴结抗辐射基质成分缺陷导致的结肠派尔集合淋巴结的持续性增生。由于肥大的结肠派尔集合淋巴结与在半抗原诱导的实验性结肠炎中所见的具有功能相似性，这种肥大被认为涉及淋巴毒素β受体信号传导。总之，数据表明Foxl1可能参与依赖于淋巴毒素/淋巴毒素β受体轴的肠道相关淋巴组织的细胞反应。
