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Mechanisms of Sensory System Development and Cellular Morphogenesis

The research program in the Deans laboratory has been established to study the developmental processes of cellular morphogenesis and patterning that occur in primary sensory systems.  Current research focuses on molecular mechanisms that are shared by the retina and inner ear.  Congenital syndromes such as Usher’s Syndrome, in which affected individuals are both blind and deaf, demonstrate the commonality between these systems and the logic behind this approach.  To do this we utilize a combination of transgenic and knockout mice, fluorescent and confocal microscopy, and molecular and cellular biology. 

Within the ear our goal is to understand how the receptor neurons facilitating hearing and balance are polarized during development.  These receptors are called hair cells extend a staircase array of stereocilia from their apical surface that is essential for the detection of sound or motion (see image 1).  Adjacent hair cells are typically oriented with their stereocilia bundles pointing in the same direction.   This organization is called planar cell polarity (PCP) and results in similar physiological responses in adjacent cells.  A striking exception occurs at the line of polarity reversal in the utricle and saccule as outlined in the accompanying figure and legend.  Hair cells on either side of the line of reversal have opposite stereocilia bundle orientations and consequently generate opposite responses to motion.  We have initiated a series of experiments designed to understand the rules governing PCP in the developing utricle and saccule, and to determine how these rules are broken at the line of reversal. 

Similarly in the retina we are interested in understanding how neurons become polarized and develop their elaborate and characteristic dendritic arbors.  During the assembly of neural circuits, newly born neurons migrate to specific locations and extend processes in stereotyped manners to contact the appropriate synaptic partners.  Ongoing research in the laboratory is designed to identify mechanisms of morphogenesis that enable retinal neurons to meet these criteria.  By understanding these developmental events we can predict how retinal circuits are altered in disease states, identify targets for pharmacological intervention, and contribute to our understanding of the biological basis of vision.