No turning,a Mouse Mutation Causing Left–Right and Axial Patterning Defects

AbstractPatterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was namedno turning (nt)because the mutant embryos fail to undergo embryonic turning.ntembryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, inntembryos, the direction of heart looping was randomized.Nodalandlefty,two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm.Lefty,which is normally also expressed in the floorplate, is not found in the prospective floorplate ofntembryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination ofsonic hedgehog, Brachyury,andHNF-3βgene expression. These studies showed that the notochord is present in the earlyntembryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest thatntmay participate in this process by modulating the notochordal expression ofHNF-3β