Welcome to the Groves Lab
Our lab uses the inner ear as a model system to address fundamental questions in developmental biology and regeneration. The transformation of a simple piece of epithelium - the otic placode - into a sensory organ of extreme morphological complexity provides an opportunity to study questions of competence, induction, pattern formation, cell-type differentiation and morphogenesis. We are using the complementary approaches of chick embryology and mouse genetics to address these problems. We have shown that the FGF and Wnt signaling pathways are critical in inducing the otic placode from embryonic ectoderm, and we are currently characterizing two novel Forkhead transcription factors that may mediate these inductive events. We are examining signaling pathways that specify the formation of the six auditory and balance sense organs of the ear and regulate the fine-grained and beautifully stereotyped pattern of sensory hair cells in these organs. We are also interested in trying to understand the mechanisms of how different sensory organs, such as the organ of Corti in the cochlea, arose during vertebrate evolution.
Sensory hair cells can be destroyed by prolonged exposure to loud noises, or by certain types of antibiotics or chemotherapy drugs. Mammalian hair cells are not replaced after damage, whereas non-mammalian vertebrates such as birds are able to achieve full functional recovery in a matter of weeks by inducing neighboring supporting cells to divide and replace lost hair cells. In an attempt to bring basic research to bear on this clinical problem, we have recently shown that supporting cells in the neonatal mouse cochlea have the capacity to divide and differentiate into hair cells, but that this capacity is largely lost by two weeks of age. This loss of regenerative capacity is due partly to changes in the regulation of cyclin-dependent kinase inhibitors such as p27Kip1. We are also investigating the role of Notch pathway-mediated lateral inhibition in preventing the production of new hair cells after injury.