The Deans Lab
B.S. 1996, Michigan State University; Ph.D. 2002, Harvard University; Postdoctoral Fellow, 2002-2008, Harvard University
Mechanisms of sensory system development and cellular morphogenesis
The goal of the Deans laboratory is to understand the development of Planar Polarity, a unique aspect of biological structure manifest by the polarized organization of cellular components within the plane of an epithelium. Planar polarity is essential for nervous system development and function, and mutations in planar polarity genes result in neural tube closure defects, altered axonal projections, and deficits in auditory and vestibular function.
Research in the laboratory is divided between two complementary systems. The first is the inner ear, which contains the mechanosensory hair cells that enable hearing and balance, and has emerged as a 'classical' model for planar polarity research. The second is the retina where we have identified unique functions for polarity proteins in the processes of dendrite formation and neuronal migration. Research in both of these areas employs knockout and transgenic mice to test planar polarity gene function and assays mutant phenotypes using modern anatomical techniques.
Inner ear development and hair cell planar polarity: In the ear planar polarity can be seen in the polarized organization of stereociliary bundles atop auditory and vestibular hair cells. Adjacent hair cells also align their stereociliary bundles to be oriented in the same direction. This organization is called Planar Cell Polarity (PCP) and has been best characterized for auditory hair cells of the cochlea. A striking exception occurs in the utricle and saccule where vestibular hair cells are patterned about a line of polarity reversal (LPR). Hair cells on either side of the LPR have opposing stereociliary bundle orientations and as a result can detect motion in opposite directions. Remarkably, the relative distribution of essential planar polarity proteins is not altered between hair cells with opposite stereociliary bundle orientations. This paradox underlies an outstanding question that drives research in the lab: How are vestibular hair cells patterned about the line of reversal?
Retinal development and dendrite morphogenesis: Our research in the retina is based upon identifying novel functions for planar polarity proteins initially discovered in Drosophila. This includes the Fat/Dachsous family of cadherins; adhesion molecules that are unusually large (>500kd) and appear to regulate cell-cell interactions. In the retina Fat cadherins control the number and position of dendrites emanating from amacrine cells. In the absence of Fat amacrine cells lose their distinctive dendritic polarity and extend ectopic dendrites towards the outer retina. Many amacrine cells are also misplaced into the ganglion cell layer indicating that another event regulated by Fat signaling is cellular migration. The net result of these changes is the appearance of dendrites in novel places and the de novo formation of ectopic synaptic layers. Ongoing research is directed at dissecting the molecular basis of Fat function that underlies these changes.
In summary: My laboratory studies questions of cellular morphogenesis and polarization using parallel experimental approaches in the inner ear and retina. Research in both of these systems is directed towards understanding the developmental mechanisms of planar polarity. Within the ear we are using a classical model, the mechanosensory hair cell, to assay the role of core PCP proteins in coordinating the orientation of adjacent cells and patterning vestibular hair cells about the LPR. One the other hand within the retina we are identifying new and unexpected functions for planar polarity molecules that include the regulation of dendrite number and cellular movements. The power of this complimentary approach is that findings in one system may guide interpretations or direct experimentation in the other.