MURINE CERBERUS HOMOLOG MCER-1 - A CANDIDATE ANTERIOR PATTERNING MOLECULE

Xenopus cerberus (Xcer) is a cytokine expressed in anterior mesendoder m overlapping and surrounding Spemann's gastrula organiser. When misex pressed in blastomeres, Xcer can induce ectopic heads with well-define d brain, cement gland, olfactory placodes, cyclopic eye, and occasiona lly liver and heart. We report here the identification of mCer-1, a mu rine gene related to cerberus. Both mCer-1 and Xcer appear to belong t o the cystine knot superfamily, which includes TGF beta s and BMPs. In Xenopus animal cap assays, mCer-1 and Xcer induced cement glands and markers of anterior neural tissue and endoderm, characteristic of BMP inhibition. furthermore, both antagonised the ventrolateral mesoderm-i nducing activity of coexpressed BMP4. In mouse embryos, mCer-1 was exp ressed at early gastrulation in a stripe of primitive endoderm along t he future anterior side of the egg cylinder, a region essential for an terior patterning. A second phase of expression was detected in anteri or embryonic mesendoderm, and by late-streak stages most of the anteri or half of the embryo was positive, except for the node and cardiac pr ogenitors. Expression was later seen in the cranial portion of the two most-recently formed somites and in two stripes within presomitic mes oderm. In embryos lacking Otx2, a homeogene with a demonstrated role i n anterior patterning, mCer-1 was still expressed in an anterior zone, although often abnormally. The data suggest that mCer-1 shares struct ural, functional, and expression characteristics with Xcer and may par ticipate in patterning the anterior of the embryo and nascent somite r egion, in part, through a BMP-inhibitory mechanism. (C) 1998 Academic Press.