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Kollmar, Richard
Assistant Professor, Molecular and Integrative Physiology
Dipl. Chem., Ludwigs-Maximilians Universität München
Ph.D., University of Wisconsin-Madison
Research Areas
Molecular Genetics of Hearing and Balance in the Zebrafish
Disorders of hearing and balance, which restrict our ability to communicate and to move about, afflict a significant percentage of our population: 30 million Americans have impaired hearing, and about two million are profoundly deaf. One in a thousand children is born with a deafness that impedes language development; another one in a thousand are stricken by heritable deafness before adulthood. One-third of those over 65 years of age have suffered a handicapping hearing loss; more than half of those over 70 experience balance problems. Environmental influences, such as noise, play an important role in hearing loss, but most of these ailments are due to genetic predisposition or disease. So far, however, we know only a small fraction of the several hundred genes that are likely to be important.
To investigate the genetic basis of the ear's operation, our group works primarily with the zebrafish, Danio rerio. Because it is also a vertebrate, its internal ears are very similar to those of humans: They exhibit the same elaborate anatomy, called the labyrinth, with distinct organs that detect sound or accelerations. They employ the same type of sensory cell, the so-called hair cell, that converts these mechanical stimuli into electrical signals. In the few known instances, they also express the same or similar genes. Furthermore, the zebrafish offers a unique combination of experimental advantages: simple husbandry, a short generation time, and large clutches of embryos; external development and optical transparency that facilitate imaging, electrophysiology, and behavioral studies; efficient methods for mutagenesis, transgenesis, and the manipulation of gene expression; and an advanced genomics infrastructure (see http://zfin.org/).
Our research focuses on two unique and essential elements of the internal ear, the otoliths and the hair bundle:
Otoliths of ray-finned fish, like otoconia of tetrapods, are acellular composites of proteins and calcium carbonate that convey linear accelerations to sensory hair cells. Otoliths nucleate early during ear development and grow throughout life; their extravagant shapes differ substantially among otolithic organs and among species. How and why do these differences arise in the same fluid compartment?
The hair bundle is the hair cell's eponymous mechano-sensitive organelle whose deflection initiates mechano-electrical transduction. Its "hairs", the so-called stereocilia, are supported by actin filaments whose number, length, and arrangement vary in a systematic and stereotypic fashion within each bundle, within and among the organs of the labyrinth, and among species. The resulting changes in stiffness and viscous drag optimize the hair cells' sensitivity and frequency selectivity. How is the hair bundle's intricate cytoskeleton assembled?
To answer these questions, we apply techniques from a variety of disciplines, such as biochemistry, molecular genetics, embryology, and physiology, to wildtype, mutant, and transgenic zebrafish.
Representative Publications
Kang, Y.J., Stevenson, A.K., Yau. P.M., Kollmar, R. 2008. Sparc Protein Is Required for Normal Growth of Zebrafish Otoliths. J. Assoc. Res. Otolaryngol., 9:436-51.
Vieira, M., Christensen, B.L., Wheeler, B.C., Feng, A.S., Kollmar, R. 2007. Survival and stimulation of neurite outgrowth in a serum-free culture of spiral ganglion neurons from adult mice. Hear. Res., 230:17-23.
Asai Y, Chan DK, Starr CJ, Kappler JA, Kollmar R, Hudspeth AJ. Mutation of the atrophin2 gene in the zebrafish disrupts signaling by fibroblast growth factor during development of the inner ear. Proc Natl Acad Sci U S A. 2006 Jun 13; 103(24):9069-74. Epub 2006 Jun 5. PMID: 16754885 [PubMed - indexed for MEDLINE]
Kollmar, R., Nakamura, S.K., Kappler, J.A., and Hudspeth, A.J. (2001) "Expression and phylogeny of claudins in vertebrate primordia," Proc. Natl. Acad. Sci. USA 98:10196-201.
Kollmar, R. (1999) "Who does the hair cell's 'do? Rho GTPases and hair-bundle morphogenesis," Curr. Opin. Neurobiol. 9:394-8.
Kollmar, R., Fak, J., Montgomery, L.G., and Hudspeth, A.J. (1997) "Hair cell-specific splicing of mRNA for the alpha1D subunit of voltage-gated Ca2+ channels in the chicken‘s cochlea," Proc. Natl. Acad. Sci. USA 94:14889-93.
Kollmar, R., Montgomery, L.G., Fak, J., Henry, L.J., and Hudspeth, A.J. (1997) "Predominance of the alpha1D subunit in L-type voltage-gated Ca2+ channels of hair cells in the chicken‘s cochlea," Proc. Natl. Acad. Sci. USA 94:14883-8.
Additional Information
Related Research (By Area):
Cell Signaling and Communication
Development
Sensory and Motor Systems
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