Greg J. Bashaw
University of Pennsylvania, PA·Neuroscience
A growing nerve cell must send its long wire, the axon, to exactly the right partner, and getting this wrong can contribute to developmental disorders of the nervous system. Many axons must cross the body's midline to link the left and right sides, which is essential for coordinated sensory and motor behavior.
- Fields
Neuroscience
Genetics
Biology
- Topics
axon guidance
midline crossing
commissural axons
- Grants
- 2 known grants, through Dec 2029
What they work on
- Define how the fly receptor Frazzled/DCC recruits and regulates the Wave Regulatory Complex, a set of proteins that builds actin filaments, during Netrin-driven axon attraction, building on studies of disease-causing human DCC variants.
- Determine how the COP9 complex, a protein-regulating machine found in a proteomic screen, works with Frazzled to control gene transcription in developing Drosophila neurons.
- Test how 15 genes that rise or fall with Frazzled levels, found by RNA sequencing of fly embryonic neurons, contribute to axon and dendrite targeting.
- Map the protein regions and identify the Nedd4 family ubiquitin ligase that Ndfip1 and Ndfip2 use to route Robo receptors to endosomes for breakdown, using molecular, cell biological and biochemical approaches.
- Examine commissural axon paths in Ndfip and Nedd4 single, double and conditional knockout mice, using antibody staining and lipophilic dye tracing in the spinal cord and brain.
- Test whether neurons from Ndfip mutant mice respond abnormally to the repellent Slit, and run genetic interaction tests and a biochemical screen to find other Ndfip targets.
More about the research
To do this, an axon first has to be drawn toward the midline and ignore signals that push it away. After crossing, it must switch and be repelled so it never crosses back. Both projects ask how guidance receptors, proteins on the axon surface that sense these cues, are controlled. One project works in fruit flies and the other in mice.
Why it matters
Understanding how neurons wire into working circuits could give insight into developmental disorders of the nervous system. It may also inform ways to promote nerve repair after injury or disease. Work on the DCC receptor may shed light on human conditions caused by faulty DCC. Guidance molecules also shape many other tissues, so the findings could inform development outside the nervous system.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Timothy M Gomez
University of Wisconsin-Madison, WI·Neuroscience
Identify which EGF-family ligands (EGF and Neuregulins) and ErbB receptors trigger growth cones to form and mature invadosomes, actin-based protrusions that degrade matrix, using gain- and loss-of-function manipulations and fluorescence imaging of cultured neurons.
Sergiu Pasca
Stanford University, CA·Neuroscience
Generate and functionally characterize human stem cell-derived organoids that resemble the spinal cord floor plate, the midline structure that guides crossing axons.
Jennifer Kong
University of Washington, WA·Biochemistry
Define the principles by which membrane-tethered E3 ubiquitin ligases, enzymes that tag proteins for destruction, recognize and target cell-surface receptors, mapping their target networks with mass spectrometry and biochemistry.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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