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Mech Dev April 1, 2013; 130 (4-5): 254-71.
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Rab GTPases are required for early orientation of the left-right axis in Xenopus.

The earliest steps of left-right (LR) patterning in Xenopus embryos are driven by biased intracellular transport that ensures a consistently asymmetric localization of maternal ion channels and pumps in the first 2-4 blastomeres. The subsequent differential net efflux of ions by these transporters generates a bioelectrical asymmetry; this LR voltage gradient redistributes small signaling molecules along the LR axis that later regulate transcription of the normally left-sided Nodal. This system thus amplifies single cell chirality into a true left-right asymmetry across multi-cellular fields. Studies using molecular-genetic gain- and loss-of-function reagents have characterized many of the steps involved in this early pathway in Xenopus. Yet one key question remains: how is the chiral cytoskeletal architecture interpreted to localize ion transporters to the left or right side? Because Rab GTPases regulate nearly all aspects of membrane trafficking, we hypothesized that one or more Rab proteins were responsible for the directed, asymmetric shuttling of maternal ion channel or pump proteins. After performing a screen using dominant negative and wildtype (overexpressing) mRNAs for four different Rabs, we found that alterations in Rab11 expression randomize both asymmetric gene expression and organ situs. We also demonstrated that the asymmetric localization of two ion transporter subunits requires Rab11 function, and that Rab11 is closely associated with at least one of these subunits. Yet, importantly, we found that endogenous Rab11 mRNA and protein are expressed symmetrically in the early embryo. We conclude that Rab11-mediated transport is responsible for the movement of cargo within early blastomeres, and that Rab11 expression is required throughout the early embryo for proper LR patterning.

PubMed ID: 23354119
Article link: Mech Dev
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: atp6v0c gal.2 kcnq1 nodal nodal1 rab11a rab11b.1 rab9a vangl2
Antibodies: Atp6v0c Ab1 Kcnq1 Ab1 Kcnq1 Ab2 Rab11a Ab1
Morpholinos: vangl2 MO1

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