The intricate neural network formation during embryonic and perinatal development is fundamental for proper brain functions. Recent aggregate data also implicates stereotyped neuronal development in specific adult brain functions through adult neurogenesis. Aberrant neural network formation has been suggested to be the cellular basis for many mental disorders. My laboratory is interested in understanding the molecular and cellular mechanisms underlying neuronal navigation during early neural development and in adulthood. We are also interested in understanding the function of risk genes of mental disorders in neural development. There are two major focuses in our research:
1. Neuronal migration and axon/dendritic development of newborn neurons from neural stem cells in the embryonic and adult brain: Although the environment in the developing brain and in the mature central nervous system (CNS) are quite different, adult neurogenesis in the hippocampus and in the olfactory bulb exhibit strikingly similar neural developmental processes to early embryonic neurogenesis, including neuronal morphogenesis and migration, axon/dendritic development and targeting, and finally synapse formation. We are particularly interested in understanding the intrinsic and extrinsic mechanisms regulating navigation of newborn neurons, including neuronal migration and axon/dendritic development in the embryonic and adult brain. In contrast to active and rapid axonal and dendritic growth of newborn neurons during adult neurogenesis, regenerative capability of mature neurons in the adult brain is extremely limited. We are interested in mechanisms promoting axon regeneration in the adult nervous system with a focus on epigenetic regulation of intrinsic growth ability.
2. Understanding mechanisms of neurological diseases and mental disorders with neural developmental origins. We are currently focusing on investigating roles of several susceptibility genes for mental disorders in regulating different phases of embryonic and adult neurogenesis, including MeCP2 (Rett Syndrome), PTEN (autism), NF1 (neurofibromatosis type 1) and DISC1 (Schizophrenia and autism) using mouse as a model system. In parallel, we are using patient-specific, induced pluripotent stem cells (iPSCs) from fibroblasts of human patients with MeCP2, DISC1 mutations as human models to study the function of these risk genes in neural development and how mutation in these risk genes contribution to the pathogenesis of diseases.
- Sun, G.J., Zhou, Y., Stadel, R.P., Mosse, J., Yong, J.H.A., Itoa, S., Kawasakia, N.K., Phana, A.T., Oha, J.H., Modaka, N., Reed, R.R., Toni, N., Song, H., and Ming, G-l. (2015). Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain. Proceedings of the National Academy of Sciences of U.S.A. 112, 9484-9
- Yoon, K.J., Nguyen, H.N., Ursini, G., Zhang, F., Kim, N-S., Wen, Z., Makri, G., Nauen, D., Shin, J.H., Park, Y., Chung, R., Pekle, E., Zhang, C., Towe, M., Hussaini S, M.Q., Lee, Y., Rujescu, D., St. Clair, D., Kleinman, J.E., Hyde, T.M., Krauss, G., Christian, K.M., Rapoport, J.L., Weinberger, D.R., Song, H-j., and Ming, G-l. (2014). Modelling a risk factor for schizophrenia in iPSCs and mice reveals neural stem cell function associated with adherens junctions and polarity. Cell Stem Cell 15, 79-91. (Cover; Preview in the same issue; highlighted in Nature Medicine).
- Wen, W., Nguyen, H.N.N., Guo, Z., Lalli, M.A., Wang, X., Su, Y., Kim, N-S., Yoon, K.J., Shin, J., Zhang, C., Makri, G., Nauen, D., Yu, H., Guzman, E., Chiang, C-H., Yoritomo, N., Kaibuchi, K., Zou, J., Christian, K.M., Cheng, L., Ross, C.A., Magolis, R.L., Chen, G., Kosik, K.S., Song, H-j., and Ming, G-l. (2014). Synaptic dysregulation in a human iPSC model of major mental disorders. Nature 515, 414-8. (Highlight in Nature Reviews Neuroscience)
- Sun, G.J., Sailor, K.A., Mahmood, Q., Chavali, N., Christian, K.M., Song, H. and Ming, G-l. (2013). Seamless reconstruction of intact adult-born neurons by serial end-block imaging reveals complex axonal guidance and development in the adult hippocampus. Journal of Neuroscience 33, 11400-11 (Cover)
- Kim, J.Y., Liu, C.Y., Zhang, F., Duan, X., Wen, Z., Song, J., Feighery, E., Lu, B., Rujescu, D., St Clair, D., Christian, K., Callicott, J.H., Weinberger, D.R., Song, H., and Ming, G-l., (2012). Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell 148(5):1051-64
- Kang, E., Burdick, K.E., Kim, J.Y., Duan, X., Guo, J.U., Sailor, K.A., Jung, D.E., Ganesan, S., Choi, S., Pradhan, D., Lu, B., Avramopoulos, D., Christian, K., Malhotra, A.K., Song, H., and Ming, G-l. (2011). Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron 72, 559-571.
- McGurk, J.S., Shim, S., Kim, J.U., Song, H., and Ming, G-l. (2011). Requirement of postsynaptic TRPC1 function in BDNF-Induced synaptic potentiation at the developing neuromuscular junction. J. Neurosci. 31, 14754-62 (Cover).
- Juopperi, T.A., Song, H., and Ming, G-l. (2011). Modeling neurological diseases using human induced pluripotent stem cells. Future Neurol. 6, 363-373.
- Bonaguidi, M.A., Wheeler, M., Shapiro, J.S., Stadel, R., Sun, G.J., Ming, G-l.*, and Song, H*. (2011). In vivo clonal analysis reveals self-renew and multipotent adult neural stem cell characteristics. Cell 145, 1142-55. * equal contribution
- Chiang, C.H., Su, Y., Wen, Z., Yoritomo, N., Ross, C.A., Margolis, R.L.*, Song, H.*, and Ming, G.L.* (2011). Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol. Psychiatry 16, 358-60 (Cover).
- Christian, K., Song, H. and Ming, G-l. (2010). Adult neurogenesis as a cellular model for psychiatric disorders. Cell Cycle 9, 637-7.
- Shim, S. and Ming, G-l. (2010). Role of channels and receptors in the growth cone during axonal regeneration. Exp. Neuro. 223:38-44.
- Shim, S., Yuan, J.P., Kim, J.Y., Zeng, W., Huang, G., Milshteyn, A., Kern, D., Muallem, S, Ming, G-l. *#, and Worley, P.F.# (2009). Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening. Neuron 64, 471-83 (*: corresponding author; #: equal contribution).
- Kim, J.Y., Duan, X., Liu, C.Y., Guo, J.U., Jang, M.H., Pow-anpongkul, N., Kang, E., Song, H-j. and Ming, G-l. (2009). DISC1 regulates new neurons development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 63, 761-73.
- Ming, G-l. and Song, H-j. (2009). DISC1 partners with GSK3 in neurogenesis. Cell 136, 990-2.
- Wang, C.J. Xiong, L., Lin, B. Shim, S. Ming, G-l., and Levchenko, A. (2008). A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues. Lab on Chip. 8, 227-37 (Cover).
- Goh, E.L., Young, J.K., Kuwako, K., Tessier-Lavigne, M., He, Z., Griffin, J.W., and Ming, G.L. (2008). Beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones. Molecular Brain 1:10.
- 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 130, 1146-58. (*: Co-corresponding authors).
- Ge, K., 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, 589-93. (*: Co-corresponding authors).
- Shim, S., Ge, S-y., Goh, E.L.K., Sailor, K., Yuan, J.P., Roderick, H.L., Bootman, M.D., Worley, P.F., Song, H-j. and Ming, G-l. (2005). XTRPC1-dependent chemotropic guidance of neuronal growth cones. Nat. Neurosci. 8, 730-735