Salk scientists find a single molecule that controls the fate of mature sensory neurons
Scientists at the Salk Institute have discovered that the role of neurons -- which are responsible for specific tasks in the brain -- is much more flexible than previously believed.
Neighboring neurons in the area of the brain known as the thalamus are shown making connections to the visual cortex (red) and the somatosensory cortex. Visible are the cell bodies (star-like cells in the lower right) and axons (arm-like extensions moving downward).
Courtesy of Andreas Zembrzycki/Salk Institute
By studying sensory neurons in mice, the Salk team found that the malfunction of a single molecule can prompt the neuron to make an "early-career" switch, changing a neuron originally destined to process sound or touch, for example, to instead process vision.
The finding, reported May 11, 2015 in PNAS, will help neuroscientists better understand how brain architecture is molecularly encoded and how it can become miswired. It may also point to ways to prevent or treat human disorders (such as autism) that feature substantial brain structure abnormalities.
"We found an unexpected mechanism that provides surprising brain plasticity in maturing sensory neurons," says the study's first author, Andreas Zembrzycki, a senior research associate at the Salk Institute.
The mechanism, a transcription factor called Lhx2 that was inactivated in neurons, can be used to switch genes on or off to change the function of a sensory neuron in mice. It has been known that Lhx2 is present in many cell types other than in the brain and is needed by a developing fetus to build body parts. Without Lhx2, animals typically die in utero. However, it was not well known that Lhx2 also affects cells after birth.
"This process happens while the neuron matures and no longer divides. We did not understand before this study that relatively mature neurons could be reprogrammed in this way," says senior author Dennis O'Leary, Salk professor and holder of the Vincent J. Coates Chair in Molecular Neurobiology. "This finding opens up a new understanding about how brain architecture is established and a potential therapeutic approach to altering that blueprint."
Scientists had believed that programming neurons was a one-step process. They thought that the stem cells that generate the neurons also programmed their functions once they matured. While this is true, the Salk team found that another step is needed: the Lhx2 transcription factor in mature neurons then ultimately controls the fate of the neuron.
In the mouse study, the scientists manipulated Lhx2 to make the switch in neuronal fate shortly after birth (when the mouse neurons are fully formed and considered mature). The team observed that controlling Lhx2 let them instruct neurons situated in one sensory area to process a different sense, thus enlarging one region at the expense of the other. The scientists don't know yet if targeting Lhx2 would allow neurons to change their function throughout an organism's life.
"This study provides proof that the brain is very plastic and that it responds to both genetic and epigenetic influences well after birth," says O'Leary. "Clinical applications for brain disorders are a long way away, but we now have a new way to think about them."
"Since this study was conducted in mice, we don't know the time frame in which Lhx2 would be operating in humans, but we know that post-birth, neurons in a baby's brain still have not settled into their final position -- they are still being wired up. That could take years," Zembrzycki says.
However, the findings may be an ingredient that contributes to the success of early intervention in some very young children diagnosed with autism, adds Zembrzycki. "The brain's wiring is determined genetically as well as influenced epigenetically by environmental influences and early intervention preventing brain miswiring may be an example of converging genetic and epigenetic mechanisms that are controlled by Lhx2."
Authors of the work are Andreas Zembrzycki, Carlos G. Perez-Garcia, and Dennis D. M. O'Leary, all of the Salk Institute for Biological Studies; and Chia-Fang Wang and Shen-Ju Chou, of the Institute of Cellular and Organismic Biology, Academia Sinica, in Taiwan.
The work was funded by the National Institutes of Health and a grant from the National Science Council, Taiwan.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.
Salk Communications | EurekAlert!
Inactivate vaccines faster and more effectively using electron beams
23.03.2017 | Fraunhofer-Institut für Organische Elektronik, Elektronenstrahl- und Plasmatechnik FEP
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Health and Medicine
23.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences