Developmental biologists at Tufts University have identified a "self-correcting" mechanism by which developing organisms recognize and repair head and facial abnormalities. This is the first time that such a mechanism has been reported for the face and the first time that this kind of flexible, corrective process has been rigorously analyzed through mathematical modeling.
Developmental biologists at Tufts University have identified a "self-correcting" mechanism by which developing organisms recognize and repair head and facial abnormalities. The research, reported in the May 2012 issue of the journal Developmental Dynamics, used a tadpole model to show that developing organisms are not genetically "hard-wired" with a set of pre-determined cell movements that result in normal facial features. Instead, the study shows that cell groups are able to measure their shape and position relative to other organs and perform the movements and remodeling needed to compensate for significant patterning abnormalities. Here three abnormal facial structures on the right side of a tadpole self-repair over time. On days 9 to 23, the branchial arch, or gill, (arrowhead) is almost flat rather than displaying the expected curvature, the right side of the jaw (arrow) is deformed, and the right eye is out of position and displays a "chocolate kiss" shape. By day 131-170, the branchial arch has become curved, the jaw displays the expected "U" shape and the right eye has moved up to align with the left eye and has a more rounded shape.
Credit: Tufts Center for Regenerative and Developmental Biology
The research, reported in the May 2012 issue of the journal Developmental Dynamics, used a tadpole model to show that developing organisms are not genetically "hard-wired" with a set of pre-determined cell movements that result in normal facial features. Instead, the process of development is more adaptive and robust. Cell groups are able to measure their shape and position relative to other organs and perform the movements and remodeling needed to compensate for significant patterning abnormalities, the study shows.
"A big question has always been, how do complex shapes like the face or the whole embryo put themselves together? We have found that when we created defects in the face experimentally, facial structures move around in various ways and mostly end up in their correct positions," said Michael Levin, Ph.D., senior author on the paper and director of the Center for Regenerative and Developmental Biology in Tufts University's School of Arts and Sciences. "This suggests that what the genome encodes ultimately is a set of dynamic, flexible behaviors by which the cells are able to make adjustments to build specific complex structures. If we could learn how to bioengineer systems that reliably self-assembled and repaired deviations from the desired target shape, regenerative medicine, robotics, and even space exploration would be transformed."
Previous research had found self-correcting mechanisms in other embryonic processes — though never in the face — but such mechanisms had not been mathematically analyzed to understand the precise dynamics of the corrective process.
"What was missing from previous studies — and to our knowledge had never been done in an animal model — was to precisely track those changes over time and quantitatively compare them," said first author Laura Vandenberg, Ph.D., post-doctoral associate at the Center for Regenerative and Developmental Biology. Such an analysis is crucial in order to begin to understand what information is being generated and manipulated in order for a complex structure to rearrange and repair itself.
Co-author with Levin and Vandenberg was Dany S. Adams, Ph.D. Adams is a research associate professor in the Department of Biology and a member of the center.
The Tufts biologists induced craniofacial defects in Xenopus frog embryos by injecting specific mRNA into one cell at the two-cell stage of development; this resulted in abnormal structures on one side of the embryos. They then characterized changes in the shape and position of the craniofacial structures, such as jaws, branchial arches, eyes, otic capsules and olfactory pits, through "geometric morphometric analysis," which measured positioning of a total of 32 landmarks on the top and bottom sides of the tadpoles.
Images of tadpoles taken at precise intervals showed that as they aged, the craniofacial abnormalities, or perturbations, became less apparent. This was particularly true for the jaws and branchial arches. Eye and nose tissue became more normal over time but varied in ability to achieve a completely expected shape and position.
Changes in the shape and position of facial features are a normal part of development, as any baby animal shows. With age, faces elongate and eyes, nose and jaws move relative to each other. But the movement is normally slight.
In contrast, the Tufts research team found that in tadpoles with severe malformations, the facial structures shifted dramatically in order to repair those malformations. It was, the researchers said, as if the system were able to recognize departures from the normal state and undertake corrective action that would not typically take place.
"We were quite astounded to see that, long before they underwent metamorphosis and became frogs, these tadpoles had normal looking faces. Imagine the implications of an animal with a severe 'birth defect' that, with time alone, can correct that defect," said Vandenberg.
Information Exchange Process
These results, say the Tufts biologists, are consistent with an information exchange process in which a structure triangulates its distance and angle from a stable reference point. While further study is needed, the researchers propose that "pings" (information-containing signals) are exchanged between an "organizing center" — such as the brain and neural network — and individual craniofacial structures.
The article points out that congenital malformations of craniofacial structures comprise a significant class of birth defects such as cleft lip, cleft palate and microphthalmia, affecting more than 1 in every 600 births. Demystifying the "face-fixing" mechanism by further research at the molecular level could inspire new approaches to correcting birth defects in humans.
"Such understanding would have huge implications not only for repairing birth defects, but also for other areas of systems biology and complexity science. It could help us build hybrid bioengineered systems, for synthetic or regenerative biology, or entirely artificial robotic systems that can repair themselves after damage or reconfigure their own structure to match changing needs in a complex environment," said Levin.
Work was supported by a National Research Service Award and funding from the National Institutes of Health and the G. Harold and Leila Y. Mathers Charitable Foundation.
Vandenberg, L. N., Adams, D. S. and Levin, M. (2012), Normalized shape and location of perturbed craniofacial structures in the Xenopus tadpole reveal an innate ability to achieve correct morphology. Dev. Dyn., 241: 863-878. doi: 10.1002/dvdy.23770
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 campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university is widely encouraged.
Kim Thurler | EurekAlert!
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences