Cdx genes and the maitenance of tissue progenitors in the mouse

Abstract

Cdx genes play important functions in the embryonic and adult life of a mouse. All three genes, Cdx1, Cdx2 and the X-linked Cdx4, are expressed during embryonic development and are essential for fetal growth. Mutations in Cdx genes cause posterior body truncations. Growth of the posterior part of the body had been shown to depend on tissue generation from progenitors with stem cell properties located at the tail end of the embryo, which we called the posterior growth zone. This growth zone is impaired in Cdx mutants, but we discovered that it is cured upon its transplantation into a wild type host embryo. Our data suggest that Cdx genes function to maintain a suitable signaling-dependent niche for the posterior tissue progenitors. Cdx genes and their relatives, the Hox genes, are necessary for proper formation of the posterior body, and work by modulating Wnt signaling. Deficiency in these genes causes body truncations and malformations of the caudal spine and uro-rectal system, a phenotype reminiscent of the “Caudal Regression Syndrome” in humans. Cdx genes are also important for other tissue progenitors in the posterior part of the embryo, the primordial germ cells, which are precursor cells for the sperm and eggs. Cdx2 inactivation early in embryonic development causes a reduction in PGC number, which can be rescued by Wnt (and Bmp) signaling. During adulthood Cdx1 and Cdx2 are expressed in the epithelium of the intestine. In organ culture studies we have shown that intestinal stem cells in Cdx2 mutants fail to populate the intestinal epithelium and cannot differentiate into intestinal derivatives, leading to a partial transformation of the intestinal into stomach-like epithelium. In summary, we have shown that Cdx genes are master regulators of progenitor pools in the developing embryos and the adult intestine.