Biologists at Tufts University have produced the first evidence that a class of proteins that make up a cell's skeleton -- tubulin proteins -- drives asymmetrical patterning across a broad spectrum of species, including plants, nematode worms, frogs, and human cells, at their earliest stages of development.
"Understanding this mechanism offers insights important to the eventual diagnosis, prevention and possible repair of birth defects that result when organs are arranged abnormally," said Michael Levin, Ph.D., senior author on the paper and director of the Center for Regenerative and Developmental Biology at Tufts University's School of Arts and Sciences.
"The research also suggests that the origin of consistent asymmetry is ancient, dating back to before plants and animals independently became multicellular organisms," he added.
The work appears in the Proceedings of the National Academy of Science Online Early Edition publishing the week of July 16, 2012.
Co-authors with Levin are Joan M. Lemire, Ph.D.,a research associate in the Department of Biology, and doctoral student Maria Lobikin, also in the Department of Biology.
Tubulin Proteins Operate Across Species
Up to now, scientists have identified cilia—rotating hair-like structures located on the outside of cells—as having an essential role in determining where internal organs eventually end up. Scientists hypothesized that during later stages of development, cilia direct the flow of embryonic fluid which allows the embryo to distinguish its right side from its left.
But it is known that many species develop consistent left-right asymmetry without cilia being present, which suggests that asymmetry can be accomplished in other ways.
Levin's team pinpointed tubulin proteins, an important component of the cell’s skeleton, or cytoskeleton. Tubulin mutations are known to affect the asymmetry of a plant called Arabidopsis, and Levin’s previous work suggested the possibility that laterality is ultimately triggered by some component of the cytoskeleton. Further, this mechanism could be widely used throughout the tree of life and could function at the earliest stages of embryonic development.
In their latest experiment, the Tufts researchers injected the same mutated tubulins into early frog embryos. The resulting tadpoles were normal, except that their internal organs’ positions were randomly placed on either the left or right side.
In subsequent experiments, collaborators at the University Of Illinois College Of Medicine and Cincinnati Children's Hospital Research Foundation found that mutated tubulins also have the same effect on left-right asymmetry of the nervous system in nematodes and on the function of human cells in culture.
Altogether, the Tufts experiment showed that tubulins are unique proteins in the asymmetry pathway that drive left-right patterning across the wide spectrum of separated species.
Importantly, mutated tubulins perturbed asymmetry only when they were introduced immediately after fertilization, not when they were injected after the first or second cell division. This suggested that a normal cytoskeleton drives asymmetry at extremely early stages of embryogenesis, many hours earlier than the appearance of cilia. Further, the Tufts biologists found that tubulins play a crucial role in the movement of other molecules to the left and right sides of the early embryo.
An Understanding of Birth Defects
"What's remarkable about these findings is that the same proteins are involved in establishing asymmetry in organisms as diverse as plants, nematodes, and frogs, and they even affect symmetry in human tissue culture cells," said Susan Haynes, Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the work. "This work is a great example of basic research that not only illuminates fundamental developmental mechanisms, but also increases our understanding of a class of serious human birth defects."
Other funding sources include the American Heart Association.
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 Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate, and professional programs across the university's schools is widely encouraged.
Alex Reid | Newswise Science News
X-ray scattering shines light on protein folding
10.07.2020 | The Korea Advanced Institute of Science and Technology (KAIST)
Surprisingly many peculiar long introns found in brain genes
10.07.2020 | Moscow Institute of Physics and Technology
New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices
Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...
Kiel physics team observed extremely fast electronic changes in real time in a special material class
In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...
Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.
Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....
Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.
Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...
A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...
07.07.2020 | Event News
02.07.2020 | Event News
19.05.2020 | Event News
10.07.2020 | Life Sciences
10.07.2020 | Materials Sciences
10.07.2020 | Life Sciences