Research Aims

        Our lab has been studying the organizing principles and developmental mechanisms governing the formation of the retinal architecture and the primary visual pathways. This work has been motivated as much by a curiosity in basic neurobiological questions as by the belief that a fundamental understanding of retinal and pathway formation will shed light on developmental disorders affecting the eye and optic projections.

        Earlier efforts within the lab had been devoted to understanding the mechanisms underlying the development of the primary visual pathway, including the fiber organization of the retinal nerve fiber layer and optic nerve, the cellular interactions controlling axonal navigation at the optic chiasm, the emergence of the chronotopic fiber re-ordering within the optic tract, and the innervation of the lateral geniculate nucleus and superior colliculus and its plasticity following early damage. Those studies clarified the rules governing pathway formation; they identified the anatomical principles by which the pathway is organized in adulthood; and they made comprehensible some of the disorders of vision that arise following injury to the optic pathway in maturity.

        More recently, our lab has been examining the transformation of an undifferentiated retinal neuroepithelium into its mature architecture, including the clonal expansion of retinal progenitors, the migratory behavior of distinct types of newborn retinal neuroblasts, the establishment of connectivity within the developing plexiform layers, and the control of naturally occurring cell death. Each of these events contributes to the sculpting of the retinal architecture, in which distinct types of neuron are generated in characteristic ratios and are positioned at different depths, interconnected via two synaptic layers.

        Superimposed upon this layered organization, certain nerve cell classes display orderly distributions in their intercellular spacing across the surface of the retina, commonly referred to as "retinal mosaics". The regularity within these retinal mosaics is a prime example of pattern formation during embryogenesis, and it is commonly presumed to reflect the precision by which cell fate determination mechanisms operate across the retina in an iterative fashion. Cell death and tangential dispersion may also contribute to the order in such mosaics, and we have recently been examining the role played by each of these in modulating the initial patterning laid down by fate-determination events.

        How neurons within such mosaics then distribute their dendrites to provide a uniform coverage of the retinal surface is also of interest, and we have very recently begun dissecting the relative contributions of the cell-intrinsic versus environmental controls of such outgrowth and overlap for different classes of neurons. Similar issues exist within the brain, but there, the presence for such patterning of nerve cells within a structure, or the extent to which their dendrites tile the volume or overlap one another have been largely unexplored. We have recently begun to extend our software tools to permit the analysis of such mosaics in three dimensions, and to relate those distributions to the 3-D morphology of cells within the mosaics.


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