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Feldheim research reveals aspects of mammalian neuronal development
Wednesday, November 23, 2005
Written by Branwyn Wagman
David Feldheim, professor of molecular, cell, and developmental biology, and his colleagues have made headway in the quest to understand neuronal development in mammals. Their research is described in the November 23 issue of Neuron.
Jena Yamada and Georgia Woods from the Felheim laboratory at UCSC contributed to the study, along with Michael Stryker, a QB3 affiliate from the Keck Foundation Center for Integrative Neuroscience at UCSF, and lab members Jianhua Cang and Megumi Kaneko.
They examined maps of the visual cortex in mice after knocking out the genes for ephrin-A2, -A3, and -A5 in all possible combinations. Feldheim explained, “The ephrins seem to be an important part of how visual connections are made during development.” These three ephrin-As account for much of the ephrin-A ligand expression in the developing visual thalamus and cortex.
In rodents, neuronal development is known to depend at least in part on the activity patterns and molecular cues carried by TC axons. The Eph family of receptor tyrosine kinases and their cell-surface-bound ligands, ephrins, are likely candidates for patterning TC axons. Eph receptors and ephrins act as positional labels in the establishment of topographic maps by triggering contact-mediated repulsion or attraction.
Feldheim and colleagues examined the results of these knockout experiments both functionally and structurally. Feldheim explained that new technology makes this possible, “We can now look at how genes affect visual connections functionally, using a new intrinsic optical imaging paradigm developed in the Stryker lab at UCSF.” The experiments demonstrate that ephrin-A ligands are required both for positioning the cortical area on the cortical plate and for internal organization within the cortical area. Knocking out all three ephrin-As shifts the visual cortex medially, rotates it, compresses it, and degrades the internal organization of its map. They present causal evidence from the ectopic expression studies that ephrin interactions occurring in the cortex and not elsewhere guide cortical maps. The study also refines understanding of how ephrin-As affect positioning.
The findings also demonstrate that two crucial aspects of map formation are dissociable. The precision of the internal order in the cortex map was affected differently in various manipulations than were the position, magnification, and orientation of the map on the cortex.
Feldheim said, “We hope that this research will ultimately apply to the study of how to regenerate neuronal connections after damage caused by injury or disease.”
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