Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada.
Dev Biol. 2010 Mar 1;339(1):155-65. doi: 10.1016/j.ydbio.2009.12.025. Epub 2010 Jan 4.
Cdx1, Cdx2 and Cdx4 encode homeodomain transcription factors that are involved in vertebral anterior-posterior (AP) patterning. Cdx1 and Cdx2 are also expressed in the intestinal epithelium during development, suggesting a role in this tissue. Intestinal defects have not been reported in Cdx1 null mutants, while Cdx2 null mutants die at embryonic day 3.5 (E3.5), thus precluding assessment of the null phenotype at later stages. To circumvent this latter shortcoming, we have used a conditional Cre-lox strategy to inactivate Cdx2 in the intestinal epithelium. Using this approach, we found that ablation of Cdx2 at E13.5 led to a transformation of the small intestine to a pyloric stomach-like identity, although the molecular nature of the underlying mesenchyme remained unchanged. Further analysis of Cdx1-Cdx2 double mutants suggests that Cdx1 does not play a critical role in the development of the small intestine, at least after E13.5.
Cdx1、Cdx2 和 Cdx4 编码同源域转录因子,参与椎体前后(AP)模式形成。Cdx1 和 Cdx2 在发育过程中也在肠道上皮中表达,提示其在该组织中的作用。Cdx1 缺失突变体未报告肠道缺陷,而 Cdx2 缺失突变体在胚胎第 3.5 天(E3.5)死亡,因此无法在后期评估缺失表型。为了克服后一个缺点,我们使用条件性 Cre-lox 策略在肠道上皮中使 Cdx2 失活。使用这种方法,我们发现 E13.5 时 Cdx2 的缺失导致小肠转化为类似于幽门胃的身份,尽管潜在间质的分子性质保持不变。对 Cdx1-Cdx2 双突变体的进一步分析表明,Cdx1 至少在 E13.5 后在小肠的发育中不起关键作用。