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
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy