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Edward Giniger, Ph.D. Adjunct Investigator Hematopoiesis Section Head Axon Guidance and Neural Connectivity Unit, NINDS B.S. Yale University, 1979 M.S. Yale University, 1979 Ph.D. Harvard University, 1988 (301) 451-3890 (301) 480-1485 ginigere@ninds.nih.gov Building 37, Room 1016A 37 Convent Dr, MSC 4270 Bethesda, MD 20892-4270 Selected Publications

Information processing in the brain is done by specialized neural circuits. Every neuron has a long process, an "axon", that carries information to its synaptic partners. Dr. Giniger's lab seeks to understand the molecular mechanisms that guide an axon, allowing it to find just the right partners from among all the myriad cells of the nervous system. His laboratory also seeks to understand why axons don't make guidance mistakes, given the intricacy of the trajectories they need to navigate. To understand these processes in humans, Dr. Giniger studies neural circuits of fruit flies, a model system that allows biochemical and cell biological approaches to be merged with classical and molecular genetics.

His laboratory has shown how a particular protein on the surface of fly nerve cells, called Notch, engages signaling proteins inside the axon that make it grow or turn when it encounters the Notch ligand-the delta protein. Notch is found in all multicellular animals, so this machinery almost certainly acts in construction of the human brain and nervous system.

Experiments from Dr. Giniger's lab also suggest that the accuracy of neural wiring arises from at least two sources. First, a transcription control protein, called Lola, coordinately regulates large collections of guidance molecules thereby establishing the balance of forces needed to specify particular axon guidance decisions precisely. Remarkably, Lola comes in 20 splice variants that probably dimerize into over one hundred different multimeric forms, all with subtly different DNA-binding properties, helping to explain how a small genome encodes the enormous diversity of axon patterning decisions. Finally, other experiments suggest that incipient guidance errors are detected in the axon, and prevented, by the action of an axonal protein kinase called Cdk5.

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Last Reviewed: October 1, 2008