The team is lead by Dr Catherine Leamey, head of the Developmental Neurobiology Laboratory of the Bosch Institute. In collaboration with colleagues from the Massachusetts Institute of Technology (MIT) and the Max-Planck institute for Biochemistry in Germany, Dr Leamey's team made a breakthrough discovery - identifying a molecule that specifically regulates the alignment of projection from both eyes. Humans normally see a single in-depth view of visual space that integrates signals from both eyes. This process is disrupted in people with visual disorders such as strabismic amblyopia. The researchers first discovered the binocular vision molecule, Ten_m3, in a screen to identify genes that are important in establishing appropriate patterns of neural connectivity in the developing visual system. They have now shown that Ten_m3 is critical for the brain to meld images from the two eyes into one useful picture in the brain. This discovery may lead to new treatments for sensory disorders in which people experience the strange phenomenon of seeing better with one eye covered. Dr Leamey started this project while undertaking her postdoctoral period at MIT in the laboratory of Professor Mriganka Sur. The project is an ongoing international collaboration, but much of the work is now undertaken in her laboratory within the Bosch Institute. Current PhD students Sam Merlin and Kelly Glendining, previous honours students Paul Lattouf and Natasha Demel, and collaborator Atomu Sawatari, also of the Bosch Institute, all contributed to the work. This work was funded by the National Health and Medical Research Council, The National Institutes of Health and the Simons Foundation.
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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.
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