Biologists hack cellular signaling to create eyes on-demand

By manipulating the natural bioelectrical communication signals that travel between cells, Tufts University scientists were able to trigger the growth of eyes on tadpoles outside of the head area. The ability to direct the growth of new organs at a particular location within a vertebrate organism could lead to significant breakthroughs in the science of regenerative medicine.

Senior author on the Tufts study, Michael Levin, said the findings break new ground in the field of biomedicine because they identify an entirely new control mechanism that can be used to induce the formation of complex organs for transplantation or regenerative applications.

The research, appearing in the journal Development, is based on the hypothesis that for every structure in the body there is a specific cellular membrane voltage range that drivesorganogenesis. To grow eyes outside of the head area, the researchers 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 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. Aside from the regenerative medicine applications of this new technique for eyes, this is a first step to cracking the bioelectric code,” explained researcher Vaibhav P. Pai.

In past research by the same group, researcher Dany S. Adams showed that bioelectrical signals are necessary for normal face formation in Xenopus (frog) embryos. In the current set of experiments, the researchers identified and marked hyperpolarized (more negatively charged) cell clusters located in the head region of the frog embryo.

The team 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 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.

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 (a class of gating proteins embedded in the membranes of the cell) which selectively allow a charged particle to pass in and out of the cell.

Using these channels, the researchers changed the membrane potential of the 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.

Following from that, the biologists were also able to show that they could control the incidence of 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.”

Pai added that the most surprising results were achieved when the team manipulated membrane voltage of cells in the tadpole’s back and tail, well outside of where the eyes could normally form. “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.”

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Source: Tufts University

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