Bastide Pauline, Darido Charbel, Pannequin Julie, Kist Ralf, Robine Sylvie, Marty-Double Christiane, Bibeau Frédéric, Scherer Gerd, Joubert Dominique, Hollande Frédéric, Blache Philippe, Jay Philippe
INSERM U661, Department of Cellular and Molecular Oncology, Centre National de la Recherche Scientifique UMR5203, Université de Montpellier I and Service d'Anatomie-Pathologie, Centre Hospitalier Universitaire Carémeau, Nimes, France.
J Cell Biol. 2007 Aug 13;178(4):635-48. doi: 10.1083/jcb.200704152.
The HMG-box transcription factor Sox9 is expressed in the intestinal epithelium, specifically, in stem/progenitor cells and in Paneth cells. Sox9 expression requires an active beta-catenin-Tcf complex, the transcriptional effector of the Wnt pathway. This pathway is critical for numerous aspects of the intestinal epithelium physiopathology, but processes that specify the cell response to such multipotential signals still remain to be identified. We inactivated the Sox9 gene in the intestinal epithelium to analyze its physiological function. Sox9 inactivation affected differentiation throughout the intestinal epithelium, with a disappearance of Paneth cells and a decrease of the goblet cell lineage. Additionally, the morphology of the colon epithelium was severely altered. We detected general hyperplasia and local crypt dysplasia in the intestine, and Wnt pathway target genes were up-regulated. These results highlight the central position of Sox9 as both a transcriptional target and a regulator of the Wnt pathway in the regulation of intestinal epithelium homeostasis.
HMG盒转录因子Sox9在肠上皮中表达，具体而言，在干细胞/祖细胞和潘氏细胞中表达。Sox9的表达需要活性β-连环蛋白-Tcf复合物，即Wnt信号通路的转录效应因子。该信号通路对肠上皮生理病理学的许多方面至关重要，但确定细胞对这种多能信号反应的过程仍有待确定。我们使肠上皮中的Sox9基因失活，以分析其生理功能。Sox9失活影响了整个肠上皮的分化，潘氏细胞消失，杯状细胞谱系减少。此外，结肠上皮的形态严重改变。我们在肠道中检测到普遍增生和局部隐窝发育异常，并且Wnt信号通路靶基因上调。这些结果突出了Sox9在调节肠上皮稳态中作为Wnt信号通路的转录靶点和调节因子的核心地位。
