The Tufts research with accompanying video and photographs will appear July 18 online in advance of publication in the journal Developmental Dynamics.
The Tufts biologists found that, before the face of a tadpole develops, bioelectrical signals (ion flux) cause groups of cells to form patterns marked by different membrane voltage and pH levels. When stained with a reporter dye, hyperpolarized (negatively charged) areas shine brightly, while other areas appear darker, creating an "electric face."
"When a frog embryo is just developing, before it gets a face, a pattern for that face lights up on the surface of the embryo," said senior author Dany S. Adams, Ph.D. Adams is a research associate professor in the Department of Biology in the Tufts School of Arts and Sciences and a member of the Tufts Center for Regenerative and Developmental Biology. "We believe this is the first time such patterning has been reported for an entire structure, not just for a single organ. I would never have predicted anything like it. It's a jaw dropper."
Tufts Post Doctoral Associate Laura N. Vandenberg, Ph.D., was first author of the paper entitled "V-ATPase-dependent ectodermal voltage and pH regionalization are required for craniofacial morphogenesis." Ryan D. Morrie, a biology major in the School of Arts and Sciences, was second author.
The discovery was a case of scientific serendipity. Adams has spent years studying bioelectrical patterning and left-right developmental differences. Her frequent research tool is a camera hooked up to a microscope that sends images to a computer.
One evening in September 2009 Adams was making time-lapse movies of early stage tadpole development. The images were coming out particularly clearly—no small achievement when filming tiny living creatures. She decided to leave the camera on overnight even though she anticipated that as the developing embryos began to move, the images would likely become too blurred to be useful.
When Adams arrived the next morning, the image on the computer monitor was out of focus as expected. But when she finished processing the rest of the images, she found they were clear. The movies were, she says, "unlike anything I had ever seen. I was completely blown away. I think I thought something like, 'OK, I know what I'll be studying for the next 20 years.'"
The imagery revealed three stages, or courses, of bioelectric activity.
First, a wave of hyperpolarization (negative ions) flashed across the entire embryo, coinciding with the emergence of cilia that enable the embryos to move. Next, patterns appeared that matched the imminent shape changes and gene expression domains of the developing face. Bright hyperpolarization marked the folding in of the surface, while both hyperpolarized and depolarized regions overlapped domains of head patterning genes. In the third course, localized regions of hyperpolarization formed, expanded and disappeared, but without disturbing the patterns created during the second stage. At the same time, the spherical embryo began to elongate.
The Tufts team found that disrupting bioelectric signaling by inhibiting ductin (a protein that is part of the machinery that transports hydrogen ions) correlated with craniofacial abnormalities. Some embryos grew two brains rather than one; others had thickened optic nerves or lacked normal nasal or jaw development. Interrupting the ion flux also altered the bioelectric patterns on the embryos' surface and expression of important face patterning mRNAs (messenger RNA that acts as a blueprint for proteins).
"Our research shows that the electrical state of a cell is fundamental to development. Bioelectrical signaling appears to regulate a sequence of events, not just one," said Laura Vandenberg. "Developmental biologists are used to thinking of sequences in which a gene produces a protein product that in turn ultimately leads to development of an eye or a mouth. But our work suggests that something else – a bioelectrical signal - is required before that can happen. "
Adams and Vandenberg note that more research is needed to discover if bioelectrical signaling works the same in frogs as in other animals, including people, and if an "electric face" exists in human development. However, they believe that study of such signaling holds great potential.
"Studying bioelectrical signaling has led us to a different, and broader, way of thinking about diseases like cancer, birth defects and tissue regeneration," Adams notes. "Potentially we can find electrical switches that turn on entire developmental cascades rather than having to find many specific tools that turn on many specific genes within that cascade, as is the current approach with gene therapy. After all, we already have tools for regulating some of these bioelectrical signals, such as drugs that prevent acid reflux by controlling potassium and hydrogen ions."
Funding for this research came from the National Institutes of Health, a NIH National Research Service Award, and a Tufts Russell L. Carpenter Summer Internship for undergraduate Ryan Morrie. Morrie will continue to work on the project as a Poskitt Fellow with the Department of Biology.
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 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.
Kim Thurler | Newswise Science News
Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen
New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
16.08.2018 | Information Technology
16.08.2018 | Health and Medicine
16.08.2018 | Information Technology