For many undergraduates the prospect of giving a journal club talk is a chore. But for Stowers associate investigator Tatjana Piotrowski, Ph.D., that presentation to a vertebrate morphogenesis class at the University of Tübingen launched her on a trans-continental journey that would define her career.
Her topic? The fish lateral line system, a subject she admits she didn’t know much about at the time. “Afterwards, I found it so interesting I arranged to work for a year in the States with an expert in the field,” says Piotrowski. “That experience got me interested in experimental embryology.”
The lateral line is a sensory system unique to aquatic vertebrates consisting of tiny hairs arrayed along the animal’s trunk that sense water motion. Movement of those hairs, which resemble hairs of the human inner ear, enables fish to orient themselves and detect other organisms in the water.
The expert who hooked Piotrowski on fish was Glenn Northcutt, a comparative neurobiologist at the Scripps Institute of Oceanography at the University of California, San Diego. Piotrowski completed her undergraduate thesis in Northcutt’s lab where in 1996 she published her first paper on the cranial nerves of a fish called the Senegalese bichir.
Side and top view of a live zebrafish larvae at five days post-fertilization.
Image: Courtesy of Dr. Tatjana Piotrowski
When she returned to Germany for graduate school, a bigger fish (impactwise) was about to take center stage in genetics—the zebrafish Danio rerio. Although the zebrafish model was pioneered in the 70’s by George Streisinger at the University of Oregon, geneticist Christiane Nüsslein-Volhard of the Max Planck Institute for Developmental Biology in Tübingen had begun the first large-scale mutagenesis screen of zebrafish. Piotrowski wanted to be part of it.
Nüsslein-Volhard agreed to take Piotrowski into her lab after a visit to the fish facility. “She liked that I was interested in fish husbandry,” said Piotrowski. “Back then, that was a very important but not very common skill!” (Shortly thereafter, Nüsslein-Volhard, along with Eric Wieschaus and Ed Lewis, won the 1995 Nobel Prize for Physiology or Medicine for the application of genetic screens to identify genes governing Drosophila development.)
In the Nüsslein-Volhard lab, Piotrowski was charged with characterizing cranio-facial mutants—close to a hundred of them—emerging from the fish screen. That effort culminated in the historic 1996 Development “zebrafish issue” in which over 40 papers—most from the Nüsslein-Volhard lab—revealed the mutant phenotypes to the world and firmly established fish as a genetic system.
Piotrowski was an author on two of those papers describing jaw and branchial arch mutants and was senior author of one. “The two years that we lived that screen was so fantastic,” she recalls. “And now—15 years later—people are still discovering what these genes encode.”
From Tübingen, Piotrowski returned to the US in 1998 to post-doc with developmental biologist Igor Dawid at the National Institutes of Health. There she began identifying genes that fell out of the Tübingen screen and searching for additional lateral line mutants that would keep her laboratory busy when she took a faculty position in 2002 at the University of Utah. Piotrowski was attracted to Utah by what she calls a superb group of developmental biologists, of which an extraordinarily large number were “fish people”.
At Utah, and now at Stowers, where she became associate investigator in 2011, Piotrowski has begun to define the signaling events that govern collective cell migration—that is, how the primordium that gives rise to lateral line structures migrates from an embryo’s head to the tail depositing sensory hair cells, or neuromasts, along the way.
Cell proliferation in a primordium of a fixed larva. Dividing cells are shown in red, cell nuclei in blue and the membranes of lateral line cells in green.
Image: Courtesy of Dr. Tatjana Piotrowski
Relevant to that, in a 2008 high-impact Developmental Cell paper, her group analyzed lateral line mutants in which Wnt signaling is perturbed to show that Wnt pathways regulate Fgf signaling to subdivide the primordium into a leading region and a trailing portion.
She is also interested in molecular mechanisms underlying regeneration, because—unlike human inner ear hair cells, which are permanently lost when damaged—neuromasts regenerate from nearby stem cells contained in the primordium. “A big question is why mammals cannot do this,” says Piotrowski. “Where is the block in signaling?”
A 2005 Neuron paper from her lab indicated that glial cells may play a role in hair cell regeneration, at least in fish, by blocking cell division and subsequent differentiation of hair stem cells. Currently, her lab is determining what those glia-derived signals may be.
Piotrowski grew up in Herrenberg near Stuttgart in Germany and says she always liked natural science. Although that could account for her interest in fish, like many embryologists, she is simply awed by watching an embryo develop. “One of the things I love about our work is the beauty of these embryos,” she says. “It is a privilege to sit at the microscope and see a single cell turn into an embryo—it is an incredibly aesthetic experience.”