Development and regeneration of the inner ear
My laboratory 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 mechansisms 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.
Selected Publications
Ohyama T, Groves AK (2004) Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis 38:195-199.
Doetzlhofer A, White PM, Johnson JE, Segil N, Groves AK (2004) In vitro growth and differentiation of mammalian sensory hair cell progenitors: a requirement for EGF and
periotic mesenchyme. Developmental Biology 272:432-447.
Ohyama T, Groves AK (2004) Expression of mouse Foxi class genes in early craniofacial development. Developmental Dynamics 231:640-646.
Brown ST, Wang J, Groves AK (2005) Dlx gene expression during chick inner ear development. Journal of Comparative Neurology 483:48-65.
Kil SH, Streit A, Brown ST, Agrawal N, Collazo A, Zile MH, Groves AK (2005) Distinct roles for hindbrain and paraxial mesoderm in the induction and patterning of the
inner ear revealed by a study of vitamin-A-deficient quail. Developmental Biology 285:252-271.
Martin K, Groves AK (2006) Competence of cranial ectoderm to respond to Fgf signaling suggests a two-step model of otic placode induction. Development
133:877-887.
Ohyama T, Mohamed OA, Taketo MM, Dufort D, Groves AK (2006) Wnt signals mediate a fate decision between otic placode and epidermis. Development 133:865-
875.
Arnold JS, Braunstein EM, Ohyama T, Groves AK, Adams JC, Brown MC, Morrow BE. (2006) Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear,
defective in 22q11DS patients. Human Molecular Genetics 15:1629-1639.
White PM, Doetzlhofer A, Lee YS, Groves AK, Segil N. (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. (2006) Nature
441:984-987.
Raft S, Koundakjian EJ, Quinones H, Jayasena CS, Goodrich LV, Johnson JE, Segil N, Groves AK (2007) Cross-regulation of Ngn1 and Math1 coordinates the production of
neurons and sensory hair cells during inner ear development. Development 134:4405-4415.
Contact Information
- Andy K. Groves, Ph.D.
- Department of Neuroscience
- Baylor College of Medicine
- One Baylor Plaza
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-3100
- Fax: (713) 798-3946
- E-mail: akgroves@bcm.edu
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