Using genetic manipulation of membrane voltage in Xenopus (frog) embryos, biologists at Tufts University's School of Arts and Sciences were able to cause tadpoles to grow eyes outside of the head area.
Changing the bioelectric voltage in embryonic frog cell in tadpole's back caused cell to develop into a functioning eye. Credit: Michael Levin and Sherry Aw
The researchers achieved most surprising results when they manipulated membrane voltage of cells in the tadpole's back and tail, well outside of where the eyes could normally form. "The hypothesis is that for every structure in the body there is a specific membrane voltage range that drives organogenesis," said Pai. "These were cells in regions that were never thought to be able to form eyes. This suggests that cells from anywhere in the body can be driven to form an eye."
To do this, they changed the voltage gradient of cells in the tadpoles' back and tail to match that of normal eye cells. The eye-specific gradient drove the cells in the back and tail—which would normally develop into other organs—to develop into eyes.
These findings break new ground in the field of biomedicine because they identify an entirely new control mechanism that can be capitalized upon to induce the formation of complex organs for transplantation or regenerative medicine applications, according to Michael Levin, Ph.D., professor of biology and director of the Center for Regenerative and Developmental Biology at Tufts University's School of Arts and Sciences. Levin is senior and corresponding author on the work published in the journal Development online December 7 2011, in advance of print.
"These results reveal a new regulator of eye formation during development, and suggest novel approaches for the detection and repair of birth defects affecting the visual system," he said. "Aside from the regenerative medicine applications of this new technique for eyes, this is a first step to cracking the bioelectric code."
Tufts post-doctoral fellow Vaibhav P. Pai Ph.D., is first author of the paper, entitled "Transmembrane Voltage Potential Controls Embryonic Eye Patterning in Xenopus laevis." .
Signals Turn On Eye Genes
From the outset of their research, the Tufts' biologists wanted to understand how cells use natural electrical signals to communicate in their task of creating and placing body organs. In recent research, Tufts biologist Dany S. Adams showed that bioelectrical signals are necessary for normal face formation in the Xenopus (frog) embryos. In the current set of experiments, the Levin lab identified and marked hyperpolarized (more negatively charged) cell clusters located in the head region of the frog embryo.
They found that these cells expressed genes that are involved in building the eye called Eye Field Transcription Factors (EFTFs). Sectioning of the embryo through the developed eye and analyzing the eye regions under fluorescence microscopy showed that the hyperpolarized cells contributed to development of the lens and retina. The researchers hypothesized that these cells turned on genes that are necessary for building the eye.
Changing the Signals Lead to Defects
Next, the researchers were able to show that changing the bioelectric code, or depolarizing these cells, affected normal eye formation. They injected the cells with mRNA encoding ion channels, which are a class of gating proteins embedded in the membranes of the cell. Like gates, each ion channel protein selectively allows a charged particle to pass in and out of the cell.
Using individual ion channels that allow, the researchers changed the membrane potential of these cells. This affected expression of EFTF genes, causing abnormalities to occur: Tadpoles from these experiments were normal except that they had deformed or no eyes at all.
Further, the Tufts biologists were also able to show that they could control the incidence of abnormal eyes by manipulating the voltage gradient in the embryo. "Abnormalities were proportional to the extent of disruptive depolarization," said Pai. "We developed techniques to raise or lower voltage potential to control gene expression."
Electric Properties of Cells Can Be Manipulated to Generate Specific Organs
The researchers achieved most surprising results when they manipulated membrane voltage of cells in the tadpole's back and tail, well outside of where the eyes could normally form.
"The hypothesis is that for every structure in the body there is a specific membrane voltage range that drives organogenesis," said Pai. "By using a specific membrane voltage, we were able to generate normal eyes in regions that were never thought to be able to form eyes. This suggests that cells from anywhere in the body can be driven to form an eye."
Levin and his colleagues are pursuing further research, additionally targeting the brain, spinal cord, and limbs. The findings, he said "will allow us to have much better control of tissue and organ pattern formation in general. We are developing new applications of molecular bioelectricity in limb regeneration, brain repair, and synthetic biology." Additional authors include post-doctoral fellow Sherry Aw, Tufts Postdoctoral Associate Tal Shomrat, and Research Associate Joan M. Lemire. Funding for this research came from the National Institutes of Health.
"Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis," Vaibhav P. Pai, Sherry Aw, Tal Shormat, Joan M. Lemire, Development, published online before print December 20, 2011,doi:10.1242/dev.073759
Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate, and professional programs across the university's schools is widely encouraged.
Alex Reid | EurekAlert!
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Power and Electrical Engineering
17.07.2018 | Life Sciences
16.07.2018 | Physics and Astronomy