Vivo-Morpholinos: Same oligos, from cultures to critters -


Serotonin has early, cilia-independent roles in Xenopus left-right patterning
Laura N. Vandenberg, Joan M. Lemire, Michael Levin


Consistent left-right (LR) patterning of the heart and viscera is a crucial part of normal embryogenesis. Because errors of laterality form a common class of birth defects, it is important to understand the molecular mechanisms and stage at which LR asymmetry is initiated. Frog embryos are a system uniquely suited to analysis of the mechanisms involved in orientation of the LR axis because of the many genetic and pharmacological tools available for use and the fate-map and accessibility of early blastomeres. Two major models exist for the origin of LR asymmetry and both implicate pre-nervous serotonergic signaling. In the first, the charged serotonin molecule is instructive for LR patterning; it is redistributed asymmetrically along the LR axis and signals intracellularly on the right side at cleavage stages. A second model suggests that serotonin is a permissive factor required to specify the dorsal region of the embryo containing chiral cilia that generate asymmetric fluid flow during neurulation, a much later process. We performed theory-neutral experiments designed to distinguish between these models. The results uniformly support a role for serotonin in the cleavage-stage embryo, long before the appearance of cilia, in ventral right blastomeres that do not contribute to the ciliated organ.



    The authors declare that they do not have any competing or financial interests.


    L.N.V. and M.L. conceived and designed the experiments. L.N.V. performed experiments. J.M.L. contributed reagents. L.N.V. and M.L. analyzed the data. L.N.V., J.M.L. and M.L. wrote and edited the manuscript.


    This work was supported by an American Heart Association Established Investigator Grant [grant number 0740088N to M.L.]; and the National Institutes of Health [grant number R01-GM077425 to M.L., fellowship F32GM087107 to L.N.V.].


    Supplementary material for this article is available at

  • Received May 21, 2012.
  • Accepted August 7, 2012.

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