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Forsyth scientists gain greater understanding of how embryos differentiate left from right

lectrical signals that ultimately control gene expression and the position of the heart and visceral organs," Levin said. "We have now identified and explored an additional component of this novel mechanism ?a protein pump that generates voltage and pH gradients. For the first time, we have a glimpse of how three different vertebrates utilize such ion flows in concert with ciliary movement and the function of pre-nervous neurotransmitters."

The findings, to be published in the May 1 issue of Development (available online on April 18th) are key for understanding human development. According to Dr. Levin, this work shows a unified model for understanding embryonic development, and is therefore likely to provide important insight into human development. "Biased left-right asymmetry is both a fascinating and medically important phenomenon," said Levin. "Problems with left/right asymmetry are responsible for a wide-range of birth defects in humans including conditions that affect the heart, the digestive system, the lungs and the brain. Building on our earlier research, we are gaining a significant understanding of asymmetry and getting closer to understanding its impact on humans. This fascinating ion pump has additional roles during development that are a goldmine of novel cellular control mechanisms."

Dr. Levin's team looked at molecular genetic and physiological characterization of a novel, early, biophysical event that is crucial for correct asymmetry: the flow of hydrogen ion or H+ flux. A pharmacological screen implicated the H+-pump H+-V-ATPase in Xenopus (frog) embryo asymmetry, where it directs left- and right-sided gene expression. The cell cytoskeleton is responsible for the LR-asymmetric localization of this pump during the first few cell cleavages in frog embryos. H+-flux across plasma membranes is thus asymmetric at the four- and eight-cell stages, and this asymmetry requires H+-V-ATPase activity. Artificially equalizing the asymmetry in H+
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Source:Forsyth Institute


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