A report in the May issue of the journal Developmental Dynamics reveals that biologists from the Tufts University have, for the first time, discovered a “self-correcting” mechanism by which developing organisms recognize and repair head and facial abnormalities.
This is the first time that this kind of flexible, corrective process has been rigorously analyzed through mathematical modeling.
The study demonstrates that developing organisms are not genetically “hard-wired”, but that the process is, instead, more flexible and robust. By using a tadpole model with a set of pre-determined cell movements that result in normal facial features, they demonstrated that cell groups can measure their shape and position in relationship to other organs, as well as performing the required movements and remodeling functions in order to compensate for important abnormalities in patterns.
Senior researcher, Michael Levin, Ph.D., director of the Center for Regenerative and Developmental Biology in Tufts University’s School of Arts and Sciences explained:
“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. 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.”
Earlier research had discovered self-correcting mechanisms in other embryonic processes, yet never in the face. These mechanisms had not been analyzed mathematically to shed a light onto the corrective process’ precise dynamics.
Leading researcher, Laura Vandenberg, Ph.D., a post-doctoral associate at the Center for Regenerative and Developmental Biology said:
“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.”
An analysis like this is vital for gaining insight into what information is being generated and manipulated so that a complex structure can rearrange and repair itself.
The team of biologists made one side of the embryos abnormal by injecting specific mRNA into one cell at the two-cell stage of development, which induced craniofacial defects in Xenopus frog embryos.
They then characterized changes of the craniofacial structures in terms of their shape and position, including jaws, eyes, branchial arches, otic capsules and olfactory pits by performing a ‘geometric morphometric analysis’ that measures the position of 32 landmarks on tadpoles’ top and bottom sides.
By taking images of tadpoles at precise intervals, the researchers observed that the craniofacial abnormalities (perturbations), in particular, in the jaws and branchial arches became less apparent as the tadpoles aged. They also noted that the tadpoles’ eye and nose tissue became more normal over time, although they did note various differences in achieving a completely expected shape and position.
In any baby animal it is a normal part of development that facial features change in terms of their shape and position. As the animal gets older, their faces elongate and their eyes, nose and jaws grow in relation to each other, even though the movement is generally fairly marginal.
The team observed, however, that in tadpoles with severe malformation, a major dramatic shift occurred in the facial structures in order to repair those malformations. They stated that it appeared as if the system was able to detect deviations from the normal state and perform corrective actions 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.”
The biologists state that the findings were consistent with an information exchange process in which a structure triangulates its distance and angle from a stable reference point. They say that although further studies are required, they suggest exchanging ‘pings’, i.e. signals that contain information between an ‘organizing center’ like the brain and neural network and individual craniofacial structures.
The researchers highlight the fact that birth defects, such as cleft lips, cleft palate and microphthalmia affect over 1 in 600 births. New approaches of correcting these birth defects that belong to the category of congenital malformations of craniofacial structures could potentially be corrected in humans by conducting further studies at the molecular level, which would shed more light on the “face-fixing” dynamics.
Levin concluded:
“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.”
Written By Petra Rattue