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  • The Company of Biologists  (2)
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  • The Company of Biologists  (2)
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  • 1
    Online Resource
    Online Resource
    The Company of Biologists ; 2010
    In:  Development Vol. 137, No. 7 ( 2010-04-01), p. 1095-1105
    In: Development, The Company of Biologists, Vol. 137, No. 7 ( 2010-04-01), p. 1095-1105
    Abstract: How embryos consistently orient asymmetries of the left-right (LR) axis is an intriguing question, as no macroscopic environmental cues reliably distinguish left from right. Especially unclear are the events coordinating LR patterning with the establishment of the dorsoventral (DV) axes and midline determination in early embryos. In frog embryos, consistent physiological and molecular asymmetries manifest by the second cell cleavage; however, models based on extracellular fluid flow at the node predict correct de novo asymmetry orientation during neurulation. We addressed these issues in Xenopus embryos by manipulating the timing and location of dorsal organizer induction: the primary dorsal organizer was ablated by UV irradiation, and a new organizer was induced at various locations, either early, by mechanical rotation, or late, by injection of lithium chloride (at 32 cells) or of the transcription factor XSiamois (which functions after mid-blastula transition). These embryos were then analyzed for the position of three asymmetric organs. Whereas organizers rescued before cleavage properly oriented the LR axis 90% of the time, organizers induced in any position at any time after the 32-cell stage exhibited randomized laterality. Late organizers were unable to correctly orient the LR axis even when placed back in their endogenous location. Strikingly, conjoined twins produced by late induction of ectopic organizers did have normal asymmetry. These data reveal that although correct LR orientation must occur no later than early cleavage stages in singleton embryos, a novel instructive influence from an early organizer can impose normal asymmetry upon late organizers in the same cell field.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2010
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    The Company of Biologists ; 2012
    In:  Disease Models & Mechanisms
    In: Disease Models & Mechanisms, The Company of Biologists
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1754-8411 , 1754-8403
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2012
    detail.hit.zdb_id: 2451104-3
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