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Michael Granato, Ph.D.

Asst Professor, Cell and Developmental Biology
1210 BRB II/III
(215) 898-2745; FAX: (215) 573-7149
email:   granatom@mail.med.upenn.edu
More information on Dr. Granato

Click here for selected publications since Dr. Granato's arrival at Penn

RESEARCH INTERESTS

RESEARCH TECHNIQUES

RESEARCH SUMMARY

We study the cellular and molecular mechanisms that govern axonal guidance and motor behavior regulation. We use the zebrafish embryos as a vertebrate model organism because it offers a powerful combination of forward genetics, molecular biology and exquisite cellular analysis. Using these techniques we like to understand how the nervous system of a developing embryo is assembled. Remember the despair caused by hour-long efforts to assemble those 1,000 piece puzzles. The challenge posed to developing embryos is much greater: in vertebrate embryos the task requires making billions of precise connections between nerve cells, as well as between nerve cells and muscles or other body tissues. To accomplish this the nerve cells axons must travel distances of up to several inches-cosmic distances for cells-through a maze of many tissues. Unlike with puzzle assembly, the consequences of failure have severe implications: without being wired properly, the nervous system does not work.

Research in the lab focuses on two aspects of nervous system assembly and function. One set of projects focuses on how motor axons find their way to their muscle targets. In genetic screens we have identified several mutants in which motor axons go astray: instead of finding their correct targets, they get lost in the maze. Through the analysis of these mutants, we have identified a specialized group of cells producing multiple signals. Each of the signals is essential for motor axons to navigate particular portions of the maze. Through positionally cloning, we have identified some of the mutated genes, and a central focus in the lab is now to understand the molecular mechanisms by which these signals direct axons.

The second set of projects focuses on neural circuits relevant to neuropsychiatric disease. To navigate their local environment, animals integrate a multitude of sensory information to appropriately modulate their motor behaviors. In vertebrates, a prominent motor behavior elicited by abrupt sensory stimuli, is the startle response. The startle response is mediated by neural architecture that appears conserved amongst vertebrates, including zebrafish and mammals. In humans, deficits in modulating the acoustic startle response are a feature of several complex genetic psychiatric disorders, including schizophrenia. The goal of our studies is to establish the zebrafish as a model system to study the genetic basis of acoustic startle response regulation and thereby to identify genetic lesions underlying abnormal motor control in psychiatric diseases.

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