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!
Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory
Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena
Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.
Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...
An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.
Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
06.08.2020 | Earth Sciences
06.08.2020 | Power and Electrical Engineering
06.08.2020 | Life Sciences