Associate Professor of Otolaryngology, Adjunct Associate Professor of Neurobiology, and Adjunct Associate Professor of Ophthalmology/Visual Sciences
Developmental Neurobiology, Hearing and Balance, Planar Cell Polarity, Axon Guidance
The goal of my laboratory is to understand cellular and molecular mechanisms that guide the development and function of the auditory and vestibular sensory organs of the inner ear. Although my primary appointment is in a clinical department, my laboratory is embedded in the Department of Neurobiology and located in BPRB. As a result, my lab members are deeply integrated within the Neuroscience and BPRB research communities.
Our research is focused on the development of the inner ear because a number of fundamental issues in developmental biology may be directly assayed using this system. Foremost are questions of Planar Cell Polarity. For example, how does a cell distinguish its left side from its right and turn to face the correct direction? Making this distinction is of paramount importance for inner ear sensory receptors because these cells detect sound and motion through the mechanical deflection of a polarized bundle of stereocilia. Mice with misoriented stereociliary bundles have measurable hearing loss and compromised vestibular function.
Other outstanding questions relate to axon guidance and circuit assembly. For example, how do inner ear neurons distinguish between the auditory and vestibular systems, and how do the circuits they form maintain the tonotopic or spatial maps encoded by the auditory or vestibular sensory receptors? Remarkably we have found that both sensory receptor innervation and cellular polarity are guided by Planar Cell Polarity signals, however the mechanisms of signal integration function differently for these two developmental events. Finally, because we are working in a peripheral sensory system and develop genetic models in the mouse, we are uniquely positioned to assay the behavioral consequences of our genetic manipulations through auditory and vestibular tests. Ongoing research is supported by two independent NIH grants that are designed to decipher Planar Cell Polarity signaling mechanisms in these two developmental contexts.
References (Selected Publications)
- Ratzan EM, Moon AM, Deans MR. “Fgf8 genetic labeling reveals the early specification of vestibular hair cell type in mouse utricle”. Development 2020 Nov 19;147(22)
- Ghimire SR, Deans MR. “Frizzled3 and Frizzled6 Cooperate with Vangl2 to Direct Cochlear Innervation by type II Spiral Ganglion Neurons”. J. Neuroscience. 2019 Oct 9;39(41):8013-8023
- Ghimire SR, Ratzan EM, Deans MR. “A non-autonomous function of the core PCP protein VANGL2 directs peripheral axon turning in the developing cochlea”. Development 2018 June 14;145(12)
- Stoller ML, Roman OR, Deans MR. "Domineering Non-Autonomy in Vangl1;Vangl2 Double Mutants Demonstrates Intercellular PCP Signaling in the Vertebrate Inner Ear". Developmental Biology 2018 May 1;437(1):17-26. doi: 10.1016/j.ydbio.2018.02.021
- Duncan JS*, Stoller ML*, Francl AF, Tissir F, Devenport D, Deans MR. "Celsr1 Coordinates the Planar Polarity of Vestibular Hair Cells During Inner Ear Development". Developmental Biology 2017, March 15; 423(2):126–137
- Cheng H*, Burroughs-Garcia J*, Birkness JE, Trinidad JC, Deans MR. "Disparate Regulatory Mechanisms Control Fat3 and P75NTR Protein Transport Through a Conserved Kif5-Interaction Domain". PLoS ONE 2016, Oct 27;11(10):e0165519
- Copley CO, Duncan JS, Liu C, Cheng H, Deans MR. “Postnatal Refinement of Auditory Hair Cell Planar Polarity Deficits Occurs in the Absence of Vangl2.” Journal of Neuroscience 2013, Aug 28; 33(35):14001-14016
- Deans MR. “A Balance of Form and Function: Planar Polarity in Development of the Vestibular Maculae.” Seminars in Cell & Developmental Biology 2013, May 24(5):490-8
- Yin H, Copley CO, Goodrich LV, Deans MR. “Comparison of Phenotypes between Different vangl2 Mutants Demonstrates Dominant Effects of the Looptail Mutation during Hair Cell Development.” PLoS ONE Feb 20, 2012, PMCID: PMC3282788
- Deans MR, Krol A, Abraira VE, Copley CO, Tucker AF, Goodrich LV. “Control of Neuronal Morphology by the Atypical Cadherin Fat3.” Neuron 2011 Sep 8;71(5):820-32, PMCID: PMC3521586