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Greg
Bashaw, Ph.D.
Associate Professor
Dept. of Neuroscience
School of Medicine
1113 BRB II/III
email: gbashaw@mail.med.upenn.edu
Click here for selected publications since Dr. Bashaw's arrival at Penn
RESEARCH INTERESTS
Molecular mechanisms of axon growth and guidance during nervous system development. We are interested specifically in how axon guidance receptors specify attractive and repulsive signals and transmit these signals to the navigating growth cone to generate a directed motile response. A second major focus of the lab is to investigate how transcription factor codes for motor neuron identity control the expression of specific axon guidance receptors. RESEARCH TECHNIQUES
Drosophila genetics, transgenic expression of axon guidance molecules, molecular and cellular biology, cell and tissue culture, biochemistry, light, fluorescent and confocal microscopy of the Drosophila embryonic CNS, FACS sorting of Drosophila motor neurons, micro-array analysis.
A confocal micrograph of several segments of the Drosophila embryonic
Central Nervious System showing a subset of interneurons (green) with
axon projections crossing the CNS midline. The entire axon scaffold is
shown in red.
Three dimensional reconstruction of a Drosophila embryo triple labeled for components of the midline and neuromuscular system. The midline glia are detected by fluorescence mRNA in situ to Netrin (green), a subset of CNS interneurons and all motor axon projections are detected by an antibody to the cell adhesion molecule Fasciclin II (red) and the muscles are detected with an antibody to muscle myosin (blue).
RESEARCH SUMMARY
How axons in the developing nervous system successfully navigate to their correct targets is a fundamental problem in neurobiology. Understanding the mechanisms that mediate axon guidance will give important insight into how the nervous system is correctly wired during development and may have implications for therapeutic approaches to developmental brain disorders and nerve regeneration. Achieving this understanding will require unraveling the molecular logic that ensures the proper expression and localization of axon guidance cues and receptors, and elucidating the signaling events that regulate the growth cone cytoskeleton in response to guidance receptor activation.
Axonal growth cones are guided
by both attractants and repellents, and these signals can be either short
or long-range. The Slit ligand and Roundabout (Robo) receptors, and the
Netrin ligand and DCC/UNC5 receptors are two important evolutionary conserved
ligand/receptor systems that contribute to proper connectivity in both
the vertebrate and invertebrate nervous systems. The goal of our research
is to dissect the signaling mechanisms downstream of attractive and repulsive
guidance receptors. The midline of the Drosophila CNS provides an ideal
system to address these questions. In Drosophila, both Netrins (NetA and
NetB) are expressed by the same midline cells, where they function largely
as attractants. This attractive function is mediated by Frazzled (Fra),
a member of the DCC/UNC-40 family of Netrin receptors. Slit, on the other
hand, functions as a midline repellent. This repulsive function is mediated
largely by Robo receptors. These molecules are also known to influence
neuronal and mesodermal cell migration, suggesting that determining their
function may have broad implications for understanding diseases of nervous
system development, many of which have their root in defective cell migration
and/or axon guidance. The research in my laboratory addresses the dynamics
of axon guidance receptor expression and signaling, and exploits the powerful
genetic and molecular approaches available in Drosophila.
KEY WORDS:
Axon guidance, Developmental neuroscience, Attraction, Repulsion
