Most animals display internal and/or external leftĝ€"right asymmetry. Several mechanisms for leftĝ€"right asymmetry determination have been proposed for vertebrates1-10 and invertebrates1,2,4,9,11-14 but they are still not well characterized, particularly at the early developmental stage. The gastropods Lymnaea stagnalis and the closely related Lymnaea peregra have both the sinistral (recessive) and the dextral (dominant) snails within a species and the chirality is hereditary, determined by a single locus that functions maternally. 15-18Intriguingly, the handedness-determining gene(s) and the mechanisms are not yet identified. Here we show that in L. stagnalis, the chiral blastomere arrangement at the eight-cell stage (but not the two-or four-cell stage) determines the leftĝ€"right asymmetry throughout the developmental programme, and acts upstream of the Nodal signalling pathway. Thus, we could demonstrate that mechanical micromanipulation of the third cleavage chirality (from the four-to the eight-cell stage) leads to reversal of embryonic handedness. These manipulated embryos grew to ĝ€∼ dextralizedĝ€™ sinistral and ĝ€∼ sinistralizedĝ€™ dextral snailsĝ€"that is, normal healthy fertile organisms with all the usual leftĝ€"right asymmetries reversed to that encoded by the mothersĝ€™ genetic information. Moreover, manipulation reversed the embryonic nodal expression patterns. Using backcrossed F 7 congenic animals, we could demonstrate a strong genetic linkage between the handedness-determining gene(s) and the chiral cytoskeletal dynamics at the third cleavage that promotes the dominant-type blastomere arrangement. These results establish the crucial importance of the maternally determined blastomere arrangement at the eight-cell stage in dictating zygotic signalling pathways in the organismal chiromorphogenesis. Similar chiral blastomere configuration mechanisms may also operate upstream of the Nodal pathway in leftĝ€"right patterning of deuterostomes/vertebrates. © 2009 Macmillan Publishers Limited. All rights reserved.
CITATION STYLE
Kuroda, R., Endo, B., Abe, M., & Shimizu, M. (2009). Chiral blastomere arrangement dictates zygotic left-right asymmetry pathway in snails. Nature, 462(7274), 790–794. https://doi.org/10.1038/nature08597
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