Investigators at St. Jude Children's Research Hospital have identified the cell that gives rise to the eye cancer retinoblastoma, disproving a long-standing principle of nerve growth and development. The finding suggests for the first time that it may one day be possible for scientists to induce fully developed neurons to multiply and coax the injured brain to repair itself.
A report of this work appears in the Oct. 19 issue of the journal “Cell.” Michael Dyer, Ph.D., an associate member in the St. Jude Department of Developmental Neurobiology, is the report’s senior author.
Retinoblastoma arises in the retina—the multi-layered, membrane lining the back of the eye that responds to light by generating nerve impulses that are carried into the brain by the optic nerve.
The immediate importance of the St. Jude finding is that it unexpectedly showed that retinoblastoma can arise from fully matured nerves in the retina called horizontal interneurons. This disproves the scientific principle that fully formed, mature nerves cannot multiply like young, immature cells, Dyer said. Human neurodegenerative disorders such as Alzheimer’s disease can occur when differentiated nerves in the brain try to multiply, and in the process, trigger a self-destruct program called apoptosis. Differentiation is the process by which cells lose their primitive, stem-cell-like properties that include the ability to grow and multiply, and instead develop specialized shapes and functions.
“For the past 100 years, it’s been ingrained among scientists that differentiated mature nerves are so elaborate that they can’t divide, and if they try to divide, they undergo apoptosis,” Dyer said. “There was no exception to this rule until now. This is the first time that anyone has shown that under certain conditions, a fully mature and differentiated nerve can undergo cell division and multiply.”
The discovery that fully differentiated horizontal interneurons can multiply to form retinoblastoma also challenges the established scientific belief that cancer cells are most aggressive when they are undifferentiated, Dyer said. For example, the leukemic cells of chronic myelogeneous leukemia (CML) are much less aggressive when they are differentiated; and it is generally not aggressive until the tumor cells sustain mutations that block differentiation.
“On the contrary, we showed that when certain genes are inactivated in the retina, horizontal neurons that are already differentiated and fully integrated into the brain can start multiplying rapidly and produce a very aggressive cancer,” Dyer said. “This opens an exciting new chapter in the study of neurons and brain tumors.”
An important implication of this finding is that if researchers were able to alter the activity of certain genes in fully developed neurons, they might be able to trigger them to multiply temporarily and replace the neighboring neurons that were lost as a result of neurodegenerative diseases such as Alzheimer’s, Dyer said. “Having nerves duplicate themselves might be more efficient than trying to stimulate nerve replacement by inserting stem cells into the brain, since the existing nerves would already be in the right place to restore missing brain cells,” he said. “However, there is still a lot of research required to determine if it is possible to control gene activity to make this approach practical.”
Dyer’s group made their discovery by developing different populations of mice whose retinas lacked one or more members of the Rb family of genes that include Rb, p107 and p130. This family of related genes is critical to the ability of an immature cell to stop dividing and begin to differentiate so it acquires certain specific characteristics required to do its job in the body.
The St. Jude researchers showed that when the mouse retina had reduced Rb family function, fully differentiated horizontal neurons could multiply while retaining all of the differentiated features of normal horizontal neurons.
As part of the study, the St. Jude team conducted microscopic and biochemical studies to prove that the multiplying cells were horizontal interneurons. Using such techniques, the researchers showed that as the horizontal interneurons multiplied their numbers up to 50-fold, they maintained their normal position in the retina as well as their normal connections to other cells.
If the horizontal interneuron cell division was allowed to proceed unchecked, highly differentiated tumors formed that resembled normal horizontal neurons. Unexpectedly, these tumors were aggressive and spread rapidly.
The investigators concluded that the Rb family’s only task is to prevent mature horizontal interneurons from multiplying as they did when they were immature cells.
Summer Freeman | EurekAlert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences