Edward S. Giniger, Ph.D.
Medical Genetics Branch
National Institute on Neurological Disorders and Stroke
B.S. Yale University
M.S. Yale University
Ph.D. Harvard University
Biography
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.
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Biography
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.
Publications
Giniger, E. How do Rho family GTPases direct axon growth and guidance? A proposal relating signaling pathways to growth cone mechanics. Differentiation, 70: 385-396. 2002. [PubMed]
Crowner, D., Le Gall, M., Gates, M.A. and Giniger, E. Notch steers Drosophila ISNb motor axons by regulating the Abl signaling pathway. Curr Biol, 13: 967-972. 2003. [PubMed]
Goeke, S., Greene, E.A., Gates, M.A., Grant, P.K., Crowner, D., Aigaki, T. and Giniger, E. Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila. Nature Neuroscience, 6: 917-924. 2003. [PubMed]
Horiuchi, T. Giniger, E. and Aigaki, T. Alternative trans-splicing of constant and variable exons of a Drosophila axon guidance gene, lola. Genes, Dev 17: 2496-2501. 2003. [PubMed]
Connell-Crowley, L., Vo, D., Luke, L., Giniger E. Drosophila lacking the Cdk5 activator, p35, display defective axon guidance, age-dependent behavioral deficits and reduced lifespan. Mech of Dev, 124(5):341-9. 2007. [PubMed]
Le Gall, M., DeMattei, C. and Giniger, E. Molecular separation of two signaling pathways for the receptor, Notch." Dev. Biol, 313:556-567. 2008. [PubMed]
J.K. Song, R. Kannan, G. Merdes, J. Singh, M. Mlodzik and E. Giniger. Disabled is a bona fide component of the Abl signaling network. Development. 137(21):3719-27. [PubMed]
Kuzina, I., Song, J.K. and Giniger, E. How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS. Development,138:1839-49. 2011. [PubMed]
Trunova, S., Baek, B. and Giniger, E. Cdk5 regulates the size of an AIS-like compartment in mushroom body neurons of the Drosophila central brain. J. Neurosci. 31:10451-62. 2011. [PubMed]
Gates, M.A., Kannan, R. and Giniger, E. A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire. Neural Development, 6:37. 2011. [PubMed]
Trunova, S. and Giniger, E. Absence of the Cdk5 activator, p35, causes adult-onset neurodegeneration in the central brain of Drosophila. Dis Model Mech, 5(2):148. 2012. [PubMed]
Shivalkar, M. and Giniger, E. Control of dendritic morphogenesis by Trio in Drosophila melanogaster. PLoS ONE, 7(3): e33737. 2012. [PubMed]
Giniger, E. Notch signaling and neural connectivity. Curr Opin Genet and Devel, 22: 339-346. 2012. [PubMed]
McLinden, K.A., Trunova, S. and Giniger, E. At the fulcrum in health and disease: Cdk5 and the balancing acts of neuronal structure and physiology. Brain Disorders and Therapy, S1:001. doi 10.4172/2168-975X.S1-001. 2012. [PubMed]
Ferreira, T. Ou, Y., Li, S., Giniger, E. and van Meyel, D. Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire. Development, 141(3):650-60. 2014. [PubMed]
Kannan, R., Kuzina, I., Wincovitch, S., Nowotarski, S.H., and Giniger, E. The Abl/Enabled signaling pathway regulates Golgi architecture in Drosophila photoreceptor neurons. Mol Biol of the Cell, 25:2993-3005. 2014. [PubMed]
Smith-Trunova, S., Prithviraj, R., Spurrier, J., Kuzina, I., Gu, Q. and Giniger. E. Cdk5 regulates developmental remodeling of mushroom body neurons in Drosophila. Dev Dynamics, 244:1550-1563. 2015. [PubMed]
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Publications
Giniger, E. How do Rho family GTPases direct axon growth and guidance? A proposal relating signaling pathways to growth cone mechanics. Differentiation, 70: 385-396. 2002. [PubMed]
Crowner, D., Le Gall, M., Gates, M.A. and Giniger, E. Notch steers Drosophila ISNb motor axons by regulating the Abl signaling pathway. Curr Biol, 13: 967-972. 2003. [PubMed]
Goeke, S., Greene, E.A., Gates, M.A., Grant, P.K., Crowner, D., Aigaki, T. and Giniger, E. Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila. Nature Neuroscience, 6: 917-924. 2003. [PubMed]
Horiuchi, T. Giniger, E. and Aigaki, T. Alternative trans-splicing of constant and variable exons of a Drosophila axon guidance gene, lola. Genes, Dev 17: 2496-2501. 2003. [PubMed]
Connell-Crowley, L., Vo, D., Luke, L., Giniger E. Drosophila lacking the Cdk5 activator, p35, display defective axon guidance, age-dependent behavioral deficits and reduced lifespan. Mech of Dev, 124(5):341-9. 2007. [PubMed]
Le Gall, M., DeMattei, C. and Giniger, E. Molecular separation of two signaling pathways for the receptor, Notch." Dev. Biol, 313:556-567. 2008. [PubMed]
J.K. Song, R. Kannan, G. Merdes, J. Singh, M. Mlodzik and E. Giniger. Disabled is a bona fide component of the Abl signaling network. Development. 137(21):3719-27. [PubMed]
Kuzina, I., Song, J.K. and Giniger, E. How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS. Development,138:1839-49. 2011. [PubMed]
Trunova, S., Baek, B. and Giniger, E. Cdk5 regulates the size of an AIS-like compartment in mushroom body neurons of the Drosophila central brain. J. Neurosci. 31:10451-62. 2011. [PubMed]
Gates, M.A., Kannan, R. and Giniger, E. A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire. Neural Development, 6:37. 2011. [PubMed]
Trunova, S. and Giniger, E. Absence of the Cdk5 activator, p35, causes adult-onset neurodegeneration in the central brain of Drosophila. Dis Model Mech, 5(2):148. 2012. [PubMed]
Shivalkar, M. and Giniger, E. Control of dendritic morphogenesis by Trio in Drosophila melanogaster. PLoS ONE, 7(3): e33737. 2012. [PubMed]
Giniger, E. Notch signaling and neural connectivity. Curr Opin Genet and Devel, 22: 339-346. 2012. [PubMed]
McLinden, K.A., Trunova, S. and Giniger, E. At the fulcrum in health and disease: Cdk5 and the balancing acts of neuronal structure and physiology. Brain Disorders and Therapy, S1:001. doi 10.4172/2168-975X.S1-001. 2012. [PubMed]
Ferreira, T. Ou, Y., Li, S., Giniger, E. and van Meyel, D. Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire. Development, 141(3):650-60. 2014. [PubMed]
Kannan, R., Kuzina, I., Wincovitch, S., Nowotarski, S.H., and Giniger, E. The Abl/Enabled signaling pathway regulates Golgi architecture in Drosophila photoreceptor neurons. Mol Biol of the Cell, 25:2993-3005. 2014. [PubMed]
Smith-Trunova, S., Prithviraj, R., Spurrier, J., Kuzina, I., Gu, Q. and Giniger. E. Cdk5 regulates developmental remodeling of mushroom body neurons in Drosophila. Dev Dynamics, 244:1550-1563. 2015. [PubMed]
Last updated: November 8, 2022