The left-right coordinator: the role of Vg1 in organizing left-right axis formation.
The asymmetries of internal organs are consistently oriented along the left-right axis in all vertebrates, and perturbations of left-right orientation lead to significant congenital disease. We propose a model in which a "left-right coordinator" interacts with the Spemann organizer to coordinate the evolutionarily conserved three-dimensional asymmetries in the embryo. The Vg1 cell-signaling pathway plays a central role in left-right coordinator function. Antagonists of Vg1 alter left-right development; antagonists of other members of the TGFbeta family do not. Cell-lineage directed expression of Vg1 protein can fully invert the left-right axis (situs inversus), can randomize left-right asymmetries, or can "rescue" a perturbed left-right axis in conjoined twins to normal orientation (situs solitus), indicating that Vg1 can mimic left-right coordinator activity. These are the first molecular manipulations in any vertebrate by which the left-right axis can be reliably controlled.
Hyatt
B A
BA
Graduate Program in Molecular, Cell, Developmental Biology, and Genetics, University of Minnesota, Minneapolis 55455, USA.
Yost
H J
HJ
D028341:Activins; D000818:Animals; D002352:Carrier Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004627:Embryonic Induction; D038681:Follistatin; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006321:Heart / Q000196:embryology*; D007265:Inhibins / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011506:Proteins; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D000099176:Noggin Protein
D028341:Activins; D002352:Carrier Proteins; D038681:Follistatin; D006023:Glycoproteins; D007265:Inhibins; D011506:Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D000099176:Noggin Protein; C513103:GDF1 protein, Xenopus