NO TURNING, A MOUSE MUTATION CAUSING LEFT-RIGHT AND AXIAL PATTERNING DEFECTS

Patterning along the left/right axes helps establish the orientation o f visceral organ asymmetries, a process which is of fundamental import ance to the viability of an organism. A Linkage between left/right and axial patterning is indicated by the finding that a number of genes i nvolved in left/right patterning also play a role in anteroposterior a nd dorsoventral patterning. We have recovered a spontaneous mouse muta tion causing left/right patterning defects together with defects in an teroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail t o undergo embryonic turning. nt embryos exhibit cranial neural tube cl osure defects and malformed somites and are caudally truncated. Develo pment of the heart arrests at the looped heart tube stage, with cardio vascular defects indicated by ballooning of the pericardial sac and th e pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate me soderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floorplate of nt embryos. This suggests t he possibility of notochordal defects. This was confirmed by histologi cal analysis and the examination of sonic hedgehog, Brachyury, and HNF -3 beta gene expression. These studies showed that the notochord is pr esent in the early nt embryo, but degenerates as development progresse s. Overall, these findings support the hypothesis that the notochord p lays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expr ession of HNF-3 beta. (C) 1998 Academic Press.