CRIPTO IS REQUIRED FOR CORRECT ORIENTATION OF THE ANTERIOR-POSTERIOR AXIS IN THE MOUSE EMBRYO

The anterior-posterior axis of the mouse embryo is established by two distinct organizing centres in the anterior visceral endoderm and the distal primitive streak(1-7). These organizers induce and pattern the head and trunk respectively, and have been proposed to be localized th rough coordinate cell movements that rotate a pre-existing pre-existin g proximal-distal axis(6,8). Here we show that correct localization of both head- and trunk-organizing centres requires Cripto(9,10), a puta tive signalling molecule that is a member of the EGF-CFC gene family(1 1,12), Before gastrulation, Cripto is asymmetrically expressed in a pr oximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. A Cripto null mutation generated by targeted gene disruption results in homozyg ous Cripto(-/-) embryos that mostly consist of anterior neuroectoderm and lack posterior structures, thus resembling a head without a trunk, Notably, markers of the head organizer are located at the distal end of the embryo, whereas markers of the primitive streak are absent or l ocalized to the proximal side. Our results indicate that Cripto signal ling is essential for the conversion of a pro;proximal-distal asymmetr y into an orthogonal anterior-posterior axis.