Neural stem cells are cells that can differentiate into different cell types in the nervous system. In the developing eye, retinal neural stem cells differentiate to form the neurons of the adult eye and form the optic nerve.
Led by Dr. Larysa H. Pevny, an assistant professor of genetics in the UNC School of Medicine, researchers discovered that expression levels of a particular neural stem cell gene, SOX2, are a critical factor that regulates the differentiation of neural stem/progenitor cells in the eye.
Their work appears in the current edition of the journal Genes & Development.
The SOX2 gene is a member of class of master genes that encode for transcription factors. Transcription factors are proteins that bind to DNA and regulate the expression of other genes
The investigators discovered that, in mice, disruption of the SOX2 gene in neural retinal stem cells leads to a kind of abnormal development of the eye called microphtalmia, or small eye. Approximately 10 percent of all human cases of microphtalmia result from mutations in the SOX2 gene.
Moreover, this study indicates that the degree to which SOX2 gene is disrupted dictates the severity of this condition.
"We found that even a reduction in normal SOX2 levels causes problems in these mice and this mimics the problems seen in humans," said Pevny.
The scientist pointed out that the problem in eye development in these mice results from loss of SOX2 mediated maintenance of the neural progenitor cell population in the eye.
According to Pevny, the study demonstrates that normal development of the eye is contingent upon having the right amount of SOX2, expressed at the right time and place. "Too little SOX2 expression results in the neural stem cell pool to aberrantly differentiate into neurons during development," Pevny said. "This disrupts the normal maintenance of the stem cell pool in the eye and disrupts the whole developmental process."
A complete loss of SOX2 expression in neural retinal progenitor cells results in the loss of the ability to either differentiate into neurons, or stay in the pluripotent state. In the pluripotent state, the cells are constantly replenished, but each cell retains the ability to differentiate into different cell types. This loss results in a block in eye formation in mice.
The manuscript also describes that one of the genes that SOX2 controls is Notch1, and loss of regulation of this gene is what is partially responsible for abnormal development of the eye. Notch1 is expressed in several other stem cell/progenitor populations. Therefore, SOX2 may play an important role in maintaining these populations as well.
In addition to highlighting a role for SOX2 in normal eye development, Pevny also stressed that this study illustrates the power of mouse genetics. "Right now, we are only in the hypothetical stage of therapeutic application of this work, but we finally have the genetic tools to actually test our hypothesis."
Other authors that contributed to the study are members of the UNC Neuroscience Center and department of genetics: Dr. Olena Taranova, a former UNC graduate student in neurobiology, now a postdoctoral scientist in the UNC Lineberger Comprehensive Cancer Center; Dr. Scott T. Magness, a postdoctoral scientist; B. Matthew Fagan, research technician; Dr.Yongquin Wu, director of the In Situ Hybridization Core Facility at the UNC Neuroscience Center; and Scott R. Hutton and Natalie Surzenko, graduate research assistants in the UNC Neurobiology Curriculum.
This work is supported by grants from the National Institutes of Health and the Christopher Reeves Paralysis Foundation
Leslie H. Lang | EurekAlert!
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg
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
22.03.2017 | Materials Sciences
22.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences