Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Gain Greater Understanding of How Embryos Differentiate Left from Right

19.04.2006


Researchers at the Forsyth Institute have discovered a new mechanism responsible for early left/right patterning, the process by which organs locate themselves on the left or right side of the body. The discovery of this novel mechanism, garnered through the study of three different vertebrates (frogs, chickens and zebrafish), marks the first time that a single common mechanism has been identified in left-right patterning in three distinct species. Such a discovery may have far-reaching implications for the understanding of craniofacial development, right-left hand preference, right/left brain dominance and a variety of birth defects in humans.

A team of Forsyth Institute scientists, led by Michael Levin, PhD, Director of the Forsyth Center for Regenerative and Developmental Biology, examined the molecular and genetic factors that control left/right asymmetry and identified a novel component: an ion transporter that creates strong natural voltage gradients and pH changes. The pump that normally acidifies subcellular compartments was shown to control embryonic laterality at very early stages. Their findings further challenged the previously held hypothesis that cilia (short hair-like structures on a cell) were the primary agents allowing an embryo to correctly position its internal organs along the left-right axis. Instead, their research showed a single asymmetry mechanism linking ciliary, serotonergic (serotonin is the chemical substance involved in transmitting signals between neurons), and ion flow mechanisms. The data was strengthened by the operation of this mechanism through all three vertebrates. This is important because prior data was very fragmented and different asymmetry-controlling systems appeared to be operating in frog/chick embryos vs. human/mouse/zebrafish embryos.

“In our previous research we showed that this developmental event happens earlier than expected in frogs by identifying an ion transporter that generates natural bioelectrical 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+ flux, by increasing or decreasing it on both sides equally, both randomized the location of the viscera without causing any other defects. To understand the mechanism of action of H+-V-ATPase, researchers isolated its two physiological functions, cytoplasmic pH and membrane voltage gradient (Vmem) regulation. Varying either pH or Vmem, independently of direct manipulation of H+-V-ATPase, caused disruptions of the normal LR pattern, suggesting important roles for both physiological parameters. V-ATPase inhibition also abolished the normal localization of serotonin at the 16-cell stage, suggesting that it helps to regulate the early flow of this important neurotransmitter. These data implicate H+-V-ATPase activity in patterning the left right axis of three different vertebrates, reveal mechanisms both upstream and downstream of its activity, and identify a novel role for this important ion transporter. Based on these observations, they proposed a detailed pH- and Vmem-dependent model of the early physiology of left/right patterning.

Michael Levin, PhD. is an Associate Member of the Staff in The Forsyth Institute Department of Cytokine Biology and the Director of the Forsyth Center for Regenerative and Developmental Biology, http://www.cellregeneration.org/. Through experimental approaches and mathematical modeling, Dr. Levin and his team examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. The lab’s investigations are directed toward understanding the mechanisms of signaling between cells and tissues that allows a living system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behavior.

About The Forsyth Institute

The Forsyth Institute is the world’s leading independent nonprofit research organization focused on oral, craniofacial and related biomedical science. Established in 1910, Forsyth’s mission is to lead the discovery, communication and application of breakthroughs in oral health and disease prevention that will significantly improve the health and well-being of the nation and the world.

Jennifer Kelly | EurekAlert!
Further information:
http://www.forsyth.org
http://www.cellregeneration.org

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>