Signaling Molecules and the Development of the Visual Cortex
2005 Seed Grant
Clifton W. Ragsdale, Ph.D.
The University of Chicago

The largest organ of the brain is the cerebral cortex, a sheet of tissue that is divided up into areas. Cortical areas are modules responsible for different functions, like vision, hearing and memory. Areas in turn contain smaller modules called columns. The different columns within each area are specialized to carry out different tasks. For example, in the primary visual area, VI, there are columns for the left eye and columns for the right eye. The structure of the columns can be changed by experience. In young animals, for example, depriving VI of vision from one eye by closing an eyelid will alter the size of the columns. The columns themselves are, however, initially established very early in development, before the onset of visual sensory experience, and despite the importance of columns for brain function, the molecules involved in making columns are completely unknown. Dr. Ragsdale proposes that an evolutionarily conserved set of signaling molecules, ones known to be responsible for making the limbs, the teeth, the face and even the areas of the cerebral cortex, are likely to be redeployed again at a later stage in embryonic development to make the columns of the cortex. In the planned work, Dr. Ragsdale’s group will isolate by molecular cloning specific markers for these developmental signaling systems and ask whether these molecules are, as predicted, involved in the development of the columns of the cortex.

Columns are a key structural feature of the cerebral cortex, and likely essential for much of cortical function in humans. For example, when an eye is deflected in a young experimental animal to create a model for strabismus, there are irreversible changes in the columns of the part of cortex responsible for vision. When these deflection is carried out in older animals, however, the columnar organization of the cortex does not change. A similar time course for visual system plasticity is seen in human development. Amblyopia (“lazy eye”), for example, responds best to intervention before 6 years of age. It is widely thought that these limits on visual system plasticity in humans are due to the limits on cortical column plasticity. Moreover, it seems likely that cortical columns and their development are important for much of the cerebral cortex. Molecular information about how cortical columns are initially generated in the embryo is therefore likely to provide broad insight into developmental disorders of brain development.

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