image: A normal mouse retina with amacrine cells labeled red and retinal ganglion cells labeled green. All of the other retinal neurons are gray. view more
Credit: Deans laboratory
San Francisco, CA, Dec. 15-19, 2012 Moscone Center, 747 Howard Street
ORGANIZING THE EYE'S NEURONS
Poster: 2342/B1205
Special Interest Subgroup: Tissue Development and Morphogenesis II
Tuesday, Dec. 18, 2012; Exhibit Halls A-C, 12:30 – 2 p.m.
Authors: A. R. Tomás and M. R. Deans
Tomás and Deans have identified a protein needed for neuron organization in the developing retina. The team says that the study helps reveal how the healthy retina — the part of the eye that detects light — is built, and will lead to a greater understanding of what goes wrong in eye disease.
In order for the eye to see, light-detecting cells must transmit information to neurons in the retina that relay the signal to the brain. One type of eye neuron, amacrine cells, pools information from the other eye neurons and directs output neurons, called retinal ganglion cells, to transmit the visual information to the brain. Normally the amacrine and retinal ganglion cells are found in distinct layers of the retina. However, when the researchers engineered mice to lack the protein Fat3 in their retinal ganglion cells, the researchers found that the amacrine cells moved into the space usually reserved for the retinal ganglion cells. The researchers also observed that the amacrine cells in these modified mice contained extra projections used to detect information from neighboring retina cells. These extra projections extended into parts of the retina where they usually aren't found.
"Studies in fruit flies show that Fat3 is important for tissue growth, but surprisingly, in the mouse retina, Fat3 has nothing to do with growth and everything to do with neuron organization and development," says Michael Deans, Ph.D., assistant professor of neuroscience and otolaryngology. Deans says they haven't determined whether loss of Fat3 in the eye's neurons affects vision yet, but the group plans to continue studies on Fat3's other roles in the eye.
MOTOR NEURON DISEASE CAUSED BY CELLULAR "TRAFFIC JAM"
Poster: 1786/B231
Special Interest Subgroup: Dynein
Tuesday, Dec. 18, 2012; Exhibit Halls A-C, 12:30 – 2 p.m.
Authors: J. Machamer, S. Collins, Y. Yang, S. Collins and T. Lloyd
Johns Hopkins researchers found that, in fruit flies, a form of motor neuron disease causes a traffic jam of cellular materials in the neurons' outer appendages. The scientists learned that the motor neurons — cells that control muscle movement — were unable to transport cargo such as signaling molecules and proteins in need of recycling from the tips of their appendages back to the main hub of the cell.
To study how motor neuron disease affects the body's neurons, researchers duplicated a genetic change found in patients with an inherited motor neuron disease. The protein affected by the genetic change, p150glued, is a piece of a transporter that delivers materials from the outer reaches of the cell to its central core. Like the people with some types of motor neuron disease, the fruit flies developed progressive paralysis and died early; they also couldn't fly. The scientists observed that in normal neurons, the cargo moved from one end of the appendages all the way back to the main hub of the cell, but in the defective neurons, the cargo at the very ends of the appendages was stuck there. The cargo along the main appendages moved normally.
"By determining what goes wrong on the cellular level in motor neuron disease, we can begin to develop therapeutics that mitigate these effects to treat the disease," says Thomas Lloyd, M.D., Ph.D., assistant professor of neurology and neuroscience at the Johns Hopkins University School of Medicine.
BASIS OF SOME INHERITED HEART DISEASE MAY BE HYPERCONTRACTED MUSCLE
Poster: 1802/B248
Special Interest Subgroup: Actin and Actin-Associated Proteins III
Tuesday, Dec. 18, 2012; Exhibit Halls A-C, 2 – 3:30 p.m.
Authors: M.C. Viswanathan, S. Haigh, J.C. Sparrow, W. Lehman and A. Cammarato
By studying flies genetically engineered to have muscle defects, scientists have taken a step toward explaining the mechanism and pathology of certain heart diseases in people. After making changes to the building blocks of the fruit fly version of a protein called troponin T, the researchers performed open-heart surgery and used microscopy to observe how the heart functioned differently than that of healthy fruit flies. Healthy fly hearts consist of a single tube that relaxes and expands to pump hemolymph — "fly blood." However, the fly hearts with the defective troponin T did not relax and expand as well as healthy fly hearts, and also stayed contracted longer during the pumping phase. "This suggests that people with similar defects in this heart muscle protein may have hypercontracted hearts that aren't able to relax, properly fill and pump as much blood through the body," says Anthony Cammarato, Ph.D., assistant professor of cardiology at the Johns Hopkins University School of Medicine.
Fruit flies with defective troponin T were also unable to fly. When the researchers examined the muscles responsible for powering their wings, they realized that the muscles were torn to shreds from chronic hypercontraction. In addition to continuing work with troponin T, Cammarato says he plans to use fruit fly genetics to look for additional drug targets that could be used to develop treatments for inherited heart disease, like muscle proteins that promote relaxation