Research Summary
Molecular Mechanisms Regulating Nerve growth and Guidance
during Development and in Adulthood
My laboratory is interested in understanding the molecular and cellular mechanisms
underlying neuronal navigation during CNS development and in adulthood. We
have developed quantitative in vitro and in vivo model systems to investigate
basic principles of nerve growth/regeneration, and axonal/dendritic guidance.
Signal transduction mechanisms underlying neuronal growth cone guidance:
We are interested in the molecular mechanisms underlying long-range growth
cone navigation by diffusible guidance cues. Using cultured mammalian neurons
and Xenopus spinal neurons, we are investigating the short-term and long-term
signaling events as well as modulation mechanisms within the growth cone triggered
by defined gradients of developmental guidance cues. Some specific questions
are:
- How can a growth cone make reliable steering decisions in response to very
small gradients (5-10 % across a neuronal growth cone)?
- How can a growth cone maintain its sensitivity toward guidance cues when
the basal level of the guidance cue increases by several orders of magnitude?
- How gradients of cytosolic effectors trigger rearrangements of cytoskeletal
structures that result in the steering responses?
 Mechanisms
regulating axon regeneration: Injured axons in the adult CNS do not
spontaneously regenerate because of the inhibitory CNS environment and the
decrease of the intrinsic ability to grow. We are currently examining the
signaling transduction mechanisms underlying growth cone responses to the
inhibitory molecules associated myelin using cultured postnatal rodent neurons.
Axonal and dendritic guidance of newborn neurons in the adult brain:
New neurons are continuously generated from adult neural stem cells in the
dentate gyrus of the hippocampus throughout life in all mammals, including
humans. They follow stereotyped patterns of neuronal migration and axon/dendrite
projections in adult CNS environment where they send their axons to the CA3
region and their dendrites toward the outer molecular layer. We are developing
in vitro and in vivo approaches to examine navigation behavior of newly generated
neurons in adult CNS environment. These studies may lead to a better understanding
of the fundamental questions about the mechanism underlying neuronal migration
and growth cone guidance. These studies may also shed light on strategies for
repair of damaged adult CNS after injury or degenerative neurological disease.
Our work is supported by grants from the Rockefeller
Brothers Fund, Whitehall Foundation, NIH (1RO1NS048271-01)
and a Basil
O'Connor Starter Scholar Award from the March
of Dimes Foundation.
Lab Members
Selected Publications
Duan, X., Chang, J.H., Ge, S-y., Faulkner, R.L., Kim, J.Y., Kitabatake, Y., Liu, X-b., Yang, C-h., Jordan, J.D., Ma, D.K., Liu, C.Y., Ganesan, S., Cheng, H.J., Ming, G-l.*, Lu, B.* and Song, H-j.* (2007). Disrupted-In-Schizophrenia 1 regulates integration of new neurons in the adult brain. Cell (In press).
Wen, Z., Han, L., Bamburg, J.R., Shim, S., Ming, G.L., Zheng, J.Q. (2007). BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin. J Cell Biol. 178, 107-19.
Ge, S., Yang, C.H., Hsu, K.S., Ming, G.L., Song, H. (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54, 559-66.
Ming, G.L. (2006). Turning by asymmetric actin. Nat Neurosci. 9, 1201-3.
Zhao, C., Teng, E.M., Summers, R.G. Jr., Ming, G.L., Gage, F.H. (2005). Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J. Neurosci. 26,3-11.
Ge, S-y., Goh. E.L.K., Sailor, K.A., Kitabatake, Y., Ming, G-l*. and Song, H-j*. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589-593.
Ming, G-l. and Song, H-j. (2005). Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 232-250.
Shim, S., Goh, E.L., Ge, S., Sailor, K., Yuan, J.P., Roderick, H.L., Bootman, M.D., Worley, P.F., Song, H., Ming, G.L. (2005). XTRPC1-dependent chemotropic guidance of neuronal growth cones. Nat. Neurosci. 8, 730-5.
Ren, X.R., Ming, G.L., Xie, Y., Hong, Y., Sun, D.M., Zhao, Z.Q., Feng, Z., Wang, Q., Shim, S., Chen, Z.F., Song, H.J., Mei, L., Xiong, W.C. (2004). Focal adhesion kinase in netrin-1 signaling. Nat. Neurosci. 7, 1204-12.
Ming, G.L., Wong, S.T., Henley, J., Yuan, X.B., Song, H.J., Spitzer, N.C., Poo, M.M. (2002). Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 411-8.
Ming, G-l., Henley, J., Tessier-Lavigne, M., Song, H-j., and Poo, M-m. (2001). Electrical activity modulates growth cone guidance by diffusible factors. Neuron 29, 441-452.
Ming, G-l., Song, H-j., Berninger, B., Inagaki, N., Tessier-Lavigne, M., and Poo, M-m. (1999). Phospholipase C-γ and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance. Neuron 23, 139-48.
Song, H-j*, Ming, G-l.*, He, Z.*, Tessier-Lavigne, M. and Poo, M-m. (1998). Conversion of neuronal growth cone responses from repulsion to attraction. Science 281, 1515-8..
Ming, G-l., Song, H-j., Berninger, B., Holt, C.E., Tessier-Lavigne, M., and Poo, M-m. (1997). cAMP-dependent growth cone guidance by netrin-1. Neuron 19, 1225-1235.
Song, H-j., Ming, G-l., and Poo, M-m. (1997). cAMP-induced switching in turning direction of nerve growth cones. Nature 388, 275-279.
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