![]() e-mail: piotrowski at neuro dot utah dot edu |
Assistant Professor of Neurobiology and Anatomy Developmental Neuroscience Molecular Neuroscience Cellular Neuroscience |
Diplom (M.A.) 1994, University of Tübingen, Germany; Ph.D. 1998, Max-Planck-Institute for Developmental Biology, Tübingen, Germany; Postdoctoral Fellow 1998-2001, National Institutes of Health.
A. The posterior lateral line placode in a 35h old live larva stained with Bodipy. The placode drops off neuromast precursors as it migrates posteriorly on the trunk.
B. Differentiated neuromast with hair bundles in a 4d old larva.
C. 5d old live larva in which the neuromasts are stained with the fluorescent dye Daspei.
RESEARCH:
Research in my laboratory aims to understand the molecular mechanisms regulating lateral line development in zebrafish by analyzing mutants affecting this process. The sensory lateral line consists of hair cells, which functionally and morphologically are very similar to the hair cells of the inner ear of higher vertebrates. In fish, the lateral line and the ear serve to detect water motion which helps the animal to orient itself in the environment. The similarity of structure and function of the hair cells in the ear and lateral line suggests that their development is based on similar genetic mechanisms. A key difference between these two sensory systems is that unlike the hair cells of the inner ear, the hair cells of the lateral line system are directly exposed to the environment and thus are accessible and amenable to experimental manipulation. Importantly, lateral line cell behavior can be observed in vivo using time-lapse microscopy. Thus, the zebrafish lateral line is an excellent model to study fundamental developmental processes underlying vertebrate nervous system development, such as cell migration, cell adhesion and stem cell regulation.
As yet, hardly anything is known about the molecular nature that underlies the development and function of this system. The sensory organs are derived from migrating neurogenic placodes that deposit sensory organ precursors as the placodes migrate toward the tail tip. The direction of migration, position and number of neuromasts is an inherent property of the placode. It is not known how the placode 'knows' where, when and how many neuromasts to deposit.
Our research focuses on the elucidation of these mechanisms by isolating the genes responsible for defects in these processes in mutants. So far, we have identified 26 mutants with defects in placode migration and patterning of neuromasts, or the function of the sensory organs proper.
Interestingly, several of the mutations that cause migration, cell adhesion and cell proliferation defects in the lateral line are known to play key roles in cancer formation and progression, suggesting that the cellular events driving cancer and lateral line formation may share a common set of molecular mechanisms. Specifically, we are currently investigating how the colon cancer gene APC is affecting cellular and molecular processes during lateral line development.
A second line of research in the lab focuses on elucidating the genetic mechanisms underlying hair cell regeneration in zebrafish. Sensory hair cell loss is the leading cause of deafness in humans, as humans are unable to regenerate hair cells. We are screening for zebrafish mutants affecting hair cell regeneration and are also performing microarray analyses to identify genetic interactions required to elicit hair cell regeneration. Results from these studies will hopefully aid in the development of treatments to induce similar regenerative responses in mammals.
Selected Publications
Kopinke, D., Sasine, J., Swift, J., Stephens, W.Z., and Piotrowski, T. (2006) Retinoic acid is required for endodermal pouch morphogenesis but not for pharyngeal endoderm specification. Dev. Dyn., 235:2695-2709.
Grant, K., Raible, D., and Piotrowski, T. (2005) Regulation of latent sensory hair cell precursors by glia in the zebrafish lateral line. Neuron, 45:69-80. reviewed in: Preview in Neuron, 45:3-5. L. Goodrich (2005). Hear, hear for the zebrafish. Dispatch in Current Biology, 15:67-70. T. Whitfield (2005). Precocious phenotypes and planar polarity. BioEssays (in press). A. Ghysen. The three sided romance of the lateral line: glia love axons love precursors love glia.
Piotrowski, T., Ahn, D., Schilling, T. F., Nair, S., Ruvinsky, I., Geisler, R., Rauch, G. J., Haffter, L. P., Zon, L. I., Foott, H., Dawid, I. B., and Ho, R. (2003) The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development, 130:5043-5052. Featured on 'Most viewed Top 10' and 'Hidden Jewel' in 'Developmental Biology' on Faculty of 1000. (http://www.facultyof1000.com).
Chien, C.-B., and Piotrowski, T. (2002) How the lateral line gets its glia. Trends in Neurosciences, 25:544-546.
Grandel, H., Lun, K., Rauch, G-J., Piotrowski, T., Houart, C., Sordino, P., Kuechler, A. M., Schulte-Merker, S., Geisler, R., Holder, N., Wilson, S., and Brand, M. (2002) Retinoic acid signaling in the zebrafish embryos is necessary to pattern the anterior-posterior axis of the CNS and to induce a pectoral fin bud. Development 129.
Piotrowski, T., and Nüsslein-Volhard, C. (2000) The endomesoderm plays an important role in segmentation of the pharyngeal arches in the zebrafish (Danio rerio). Dev. Biol. 225:339-356.
Bartsch, P., Gemballa, S., and Piotrowski, T. (1997) The embryonic development of Polypterus senegalus Cuvier, 1829: its staging with reference to external and skeletal features, behaviour and locomotory habits. Acta Zoologica (Stockholm) 78, No. 4, pp. 309-328.
Piotrowski, T., Schilling, T. F., Brand, M., Jiang, Y-J., Heisenberg, C. P., Beuchle, D., Grandel, H., van Eeden, F. J. M., Furutani-Seiki, M., Granato, M., Haffter, P., Hammerschmidt, M., Kane, D. A., Kelsh, R. N., Mullins, M. C., Odenthal, J., Warga, R. M., and Nüsslein-Volhard, C. (1996) Jaw and branchial arch mutants in zebrafish II: anterior arches and cartilage differentiation. Development 123:345-356.
Schilling, T. F., Piotrowski, T., Grandl, H., Brand, M., Jiang, Y-J., Heisenberg, C.-P., Beuchle, D., van Eeden, F. J. M., Furutani-Seiki, M., Granato, M., Haffter, P., Hammerschmidt, M., Kane, D. A., Kelsh, R. N., Mullins, M . C., Odenthal, J., and Nüsslein-Volhard, C. (1996) Mutations affecting the development of the jaw and branchial arches I: Gill arches. Development 123:329-344.
Piotrowski, T., and Northcutt, R. G. (1996) The cranial nerves of the Senegal bichir, Polypterus senegalus (Osteichthyes; Actinopterygii, Cladistia). Brain, Behavior and Evolution 47:55-102.
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