Hongjun Song, Ph.D. Associate Professor of Neurology / Institute for Cell Engineering Johns Hopkins University School of Medicine 733 N. Broadway, BRB #735 (office); #706 (Lab) Baltimore, MD 21205 Phone: 443-287-5612 (Lab) 443-287-7499 (Off) Fax: 410-614-9568 Email: shongju1@jhmi.edu Neuroscience webpage

Research Summary

Mechanisms Regulating Adult Mammalian Neural Stem Cells and Neurogenesis

Neurogenesis occurs throughout life in the dentate gyrus of the hippocampus where adult neural stem cells proliferate and give rise to functionally integrated granule cells. We are interested in understanding the cellular and molecular mechanisms that regulate de-differentiation and differentiation of adult neural stem cells, and migration, guidance and synaptic integration of their neuronal progeny in the mature central nervous system. Our laboratory is using an integrated approach to study rodent and human neural stem cells in cell culture and in animal models utilizing technologies in molecular biology, cell biology, biochemistry, virology, histology, multiphoton confocal imaging and electrophysiology.

1. De-differentiation and differentiation of adult neural stem cells: We have derived adult neural stem cells from transgenic animals expressing EGFP under the control of specific promoters for pluripotent genes or neuronal genes. We are currently investigating mechanisms that control the reprogramming of multipotent adult neural stem cells into pluoripotent cells as well as differentiation of adult neural stem cells into different neuronal subtypes.
2. Axonal/dendritic development and guidance by newborn neurons from adult neural stem cells: In collaboration with Dr. Guo-li Ming’s laboratory, we have developed several model systems to examine the navigation of newborn neurons in the adult brain. We are using growth cone turning assay to examine growth cone responses of labeled newborn neurons from adult transgenic mice to defined diffusible gradients of guidance cues. In parallel, we are examining migration, axonal/dendritic development and guidance of newborn neurons by manipulation of endogenous neural progenitors with engineered retrovirus in genetically modified mouse in vivo.
3. Synaptic integration and plasticity by neuronal progeny of adult neural stem cells: We have developed retroviral vectors for both loss-of-function and gain-of-function analysis of individual newborn neurons in the adult brain in vivo. We are currently examining the cellular and molecular mechanisms that regulate the functional integration and plasticity of newborn neurons using electrophysiology and multiphoton confocal imaging approaches.
4. Adult neurogenesis as a model for understanding human brain disorders: Adult neurogenesis recapitulates neuronal developmental process in a mature central nervous system environment. Interestingly, the neuronal integration process for adult born neurons is significantly prolonged compared to those during fetal development. This offers a unique opportunity to examine in detail the sequential events involved in the formation, maturation and maintenance of both GABAergic and glutamatergic synapses in vivo. We are currently focusing on several genes that have been identified or implicated in specific human disorders to examine their roles in different phases of adult neurogenesis, such as MeCP2 (Rett Syndrome), DSCAM (Down Syndrome) and DISC1 (Schizophrenia).

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).

Ge, S-y., Yang, C., Hsu. K.S., Ming, G-l. and Song, H-j. (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 24, 54, 559-66.

Ge, S-y., Pradhan, D., Ming, G-l., and Song, H-j. (2007). GABA sets the tempo for activity-dependent adult neurogenesis. TINS 30, 1-8.

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.

Lie, D.C., Colamarino, S.A., Song, H-j., Mira, H., Consiglio, A., Desire, L., Lein, E.S., Dearie, A.R., Lansford, H., and Gage, F.H. (2005). Wnt signaling regulates adult hippocampal neurogenesis. Nature 437,1370-5.

Ming, G-l. and Song, H-j. (2005). Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 232-250.

Ma, D-k., Ming, G-l., and Song, H-j. (2005). Glial influences on stem cell development: cellular niches in adult neurogenesis. Curr. Opin. Neurobio. 15, 514-520 (Cover).

Song, H-j., Stevens, C.F. and Gage, F.H. (2002). Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat. Neurosci. 5, 438-45.

Song, H-j., Stevens, C.F. and Gage, F.H. (2002). Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39-44.