Katie Kindt, Ph.D.
Figure 1: Scanning electron
micrograph of zebrafish lateral
line hair bundles. The skin of the
fish is colored gray, the actin-filled
stereocilia blue, and the primary
cilia (kinocilia) are colored orange.
Section on Sensory Cell Development and Function
Porter Neuroscience Research Center
35A Convent Drive 1D-933
Bethesda, MD 20892-3729 for U.S. Postal Service
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Telephone: (301) 443-2626 (office)
Dr. Kindt received a B.S. degree in Molecular Biology and Biochemistry from the University Wisconsin-Eau Claire, and a Ph.D. in Biomedical Sciences from the University of California-San Diego, where she studied the function and development of mechanosensory circuits in Caenorhabditis elegans in the laboratory of William Schafer. During a postdoctoral fellowship with Teresa Nicolson at the Vollum institute she used a combination of scanning electron microscopy in vivo calcium imaging to investigate the role of the primary cilium in developing hair cells (Figure 1). Dr. Kindt joined the NIDCD as an investigator in 2013. Her laboratory uses molecular and microscopy-based methods to examine sensory cell function and development in the zebrafish model system.
The Section on Sensory Cell Development and Function investigates how discrete subcellular signals, such as Ca2+ influx and vesicle release, shape hair cell development, and how these signals are required for proper physiological function.
To study hair cell development and function we use the zebrafish as a model system. Similar to mammals, zebrafish have sensory hair cells that enable them to sense sound and maintain proper balance. Previous work has shown that the same genes that cause deafness in zebrafish are associated with hearing defects in humans and in mice. In contrast to mammals the embryonic and larval zebrafish routinely studied are transparent and develop externally, therefore hair cells in zebrafish can be studied in vivo (Figure 2).
Figure 2: Transgenic illuminates sensory hair cells in the larval zebrafish. Zebrafish
have hair cells in their inner ear (A, B) and in their lateral line system (A,C). The
lateral line system is composed of clusters of superficial hair cells called neuromasts
that are readily visualized and physically stimulated.
In hair cells, mechanosensitive responses are shaped by distinct sources of Ca2+: mechanosensitive Ca2+ -permeable channels in the hair bundle, voltage-gated Ca2+ channels at the synapse, and Ca2+ storage and release from mitochondria and ER. All of these Ca2+ signals shape vesicle release and are ultimately required for the proper formation and function of hair cells. To examine these complex signals in vivo, we use transgenic zebrafish to precisely monitor Ca2+ signals in the hair cell cytoplasm, hair bundle, presynaptic density, and monitor synaptic vesicle release (Figure 3). We combine in vivo imaging of Ca2+ and vesicle fusion, confocal and electron microscopy, genetics, and pharmacology to characterize how discrete signals shape sensory function and development in an intact system. This long-term goal of this research is to improve our understanding of how hair cells functionally develop. This knowledge may provide insight into properly regenerating hair cells after they are lost, a major barrier to restoring hearing loss.
Figure 3: Localized expression of genetically encoded indicators. Genetically encoded
indicators localized to the ribbon synapse (A), hair bundle (B), and synaptic
vesicles (green) and ribbon synapses (red) (C).
- Clemens-Grisham R, Kindt KS, Schmidt B, Nicolson T. Mutations in ap1b1 cause mistargeting of the Na+/K+-ATPase pump in sensory hair cells. PLoS One. 2013 8(4): e60866
- Sheets L, Kindt KS, Nicolson T. Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. J Neurosci., 2012 32: 17273-17286.
- Kindt KS, Finch G, Nicolson T. Kinocilia mediate mechanosensitivity in developing zebrafish hair cells. Dev. Cell, 2012 23: 329-41.
- Kindt KS, Quast K, Giles A, Hendrey D, Nicastro I, Rankin C, Schafer W. Dopamine Mediates Context-Dependent Modulation of Sensory Plasticity in C elegans. Neuron, 2007 4: 662-76.
- Kindt KS*, Viswanath V*, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR. Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat. Neurosci., 2007 10: 568-77.
- Kindt KS*, Tam T*, Whiteman S, Schafer WR. Serotonin promotes G(o)-dependent neuronal migration in Caenorhabditis elegans. Curr Biol., 2002. 12: 1738-47.
*Indicates equal contribution to the work in this publication.