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Neural Regeneration Laboratory

Lab Interests | Techniques | Publications | Contacts

The Neural Regeneration Laboratory has primary interests in the areas of

regulation of adult neural stem cell differentiation
regulation of neurite outgrowth and axonal regeneration
regulation of astrocytic gliosis

One of the reasons why injury or disease of the brain and spinal cord results in permanent disability is because nerve cells (neurons) die and those that remain can rarely reform the correct wiring of the nervous system to restore function. We are undertaking several projects that examine regulation of adult neural stem cell differentiation into neurons and regulation of neurite outgrowth and axonal regeneration.

Ann Turnley

Group Leader
Associate Professor Ann Turnley

Research Fellows
Dr Adam Cole
Dr Kirsty Dixon

Research Assistants
Ms Alisa Turbic

Graduate Students
Ms Kathryn Munro (PhD student)
Ms Rachel Uren (PhD student)

Major Lab Interests

Regulation of adult neural stem cell differentiation
Regulation of neurite outgrowth and axonal regeneration
Regulation of astrocytic gliosis

Injury and diseases of the central nervous system (CNS), such as stroke, Epilepsy, Parkinson’s, Huntington’s and Alzheimer’s disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, a substantial body of evidence in recent years, including the discovery of neural stem cells, as well as an increasing understanding of factors that regulate neuron life and death, neurogenesis, neurite outgrowth and synapse formation has led to the view that repair of the central nervous system may indeed be a possibility. Effective neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement of lost neurons by differentiation of neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation of correct synaptic connections, as well as regulation of the glial response to injury. An understanding of factors that regulate these processes is still currently limited but beginning to be elucidated and has been the focus of our research for the last few years.

We are actively investigating and have projects available in each of these areas:

Comparison of neural stem cell differentiation in normal mice and mice transgenic and null mutant for genes that may be involved in promoting or inhibiting neurogenesis
Analysis of neuronal and glial differentiation in vitro in response to various cytokines and growth factors
Analysis of signal transduction pathways that may be involved in neural stem cell differentiation
Examination of factors involved in CNS regeneration after injury
Analysis of signal transduction pathways that may be involved in neurite outgrowth and dendrite/axon formation
Analysis of neurite outgrowth in primary neuronal culture and in normal and mutant mouse brains
Analysis of factors regulating astrocytic gliosis using in vitro culture systems and animal models

Techniques used

Culture and analysis of primary cells and cell lines
Neural differentiation assays
Proliferation assays
Cell Survival assays
Immunostaining of cultured cells
Immunohistochemistry of neural tissue from embryonic and adult mice
- paraffin and frozen sections
Cell counting (in vitro and in situ)
Neurite measurement
Transfection
Image analysis
cDNA subcloning
PCR, RT-PCR
Northern blotting
Western blotting/IP

Salient recent publications

McLenachan, S., Lum, M., Waters, M.J. and Turnley, A.M. (2009). Growth Hormone Promotes Proliferation of Adult Neurosphere Cultures. Growth Hormone and IGF Research in press.

Lum M., Turbic, A. Mitrovic, B. and Turnley, A.M. (2009). FGF9 inhibits astrocyte differentiation of adult mouse neural progenitor cells. J. Neurosci. Res. in press

Lum M., Croze E., Wagner C., McLenachan S., Mitrovic B. and Turnley A.M. (2009). Inhibition of neurosphere proliferation by IFNg but not IFNb is coupled to neuronal differentiation. J. Neuroimmunol. 206:32-38.

McLenachan, S., Goldshmit, Y., Fowler, K.J., Voullaire, L., Holloway, T.P., Turnley, A.M., Ioannou P.A. and Sarsero, J.P. (2008). Transgenic mice expressing the peripherin-green genomic reporter display intrinsic peripheral nervous system fluorescence. Transgenic Research 17:1103-1116.

Ransome M. and Turnley A.M. (2008). Erythropoietin promotes axonal growth in a model of neuronal polarization. Mol. Cell. Neurosci. 38:537-547.

Ransome M. and Turnley, A.M. (2008). Growth hormone signaling and hippocampal neurogenesis: insights from genetic models. Hippocampus 18: 1034-1050

Dottori, M., Leung, J., Turnley, A.M. and Pebay A. (2008). Lysophosphatidic acid inhibits neuronal differentiation of neural stem/progenitor cells derived from human embryonic stem cells. Stem Cells 26: 1146-1154.

Goldshmit, Y., Lythgo, N., Galea, M.P. and Turnley, A.M. (2008). Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. J. Neurotrauma 25:449-466.

Malaterre, J., Mantamadiotis, T., Dworkin, S., Lightowler, S., Yang, Q., Ransome, M.I., Turnley, A.M., Nichols, N., Emambokus, N.R., Frampton, J. and Ramsay, R.G. (2008). c-Myb is required for neural progenitor cell proliferation and maintenance of the neural stem cell niche in adult brain. Stem Cells 26:173-181.

Ransome, M.I. and Turnley, A.M. (2007). Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis. J. Neurochem. 102, 1953-1965.

Klein, R., Brown, D and Turnley A.M. (2007). Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model. BMC Neuroscience 8:61.

Goldshmit, Y., Galea, M.P., Bartlett, P.F. and Turnley, A.M. (2006). EphA4 regulates CNS vascular formation. J. Comp. Neurol. 97, 864-875.

Smith, P.D., McLean, K.J., Murphy, M.A., Turnley, A.M. and Cook, M.J. (2006). Functional dentate gyrus neurogenesis in a rapid kindling seizure model. Eur. J. Neurosci. 24, 3195-3203.

Canty, A.J., Greferath, U., Turnley, A.M., Murphy, M. (2006) EphA4 is required for the topographic mapping of the corticospinal tract. Proc. Natl. Acad. Sci. USA. 103, 15629-15634.

Scott H., Stebbing, M.J. Walters, C.E., McLenachan, S., Ransome, M.I. Nichols, N.R. and Turnley, A.M. (2006). Differential effects of SOCS2 on neuronal differentiation and morphology. Brain Research 1067, 138-145.

Goldshmit, Y., Galea, M.P., Bartlett, P.F. and Turnley, A.M. (2006). EphA4 regulates CNS vascular formation. J. Comp. Neurol. 97, 864-875.

Goldshmit Y., McLenachan, S. and Turnley, A.M. (2006). Role of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev. in press accepted 24/04/06.

Smith, P.D., McLean , K.J., Murphy, M.A., Turnley, A.M. and Cook, M.J. (2005). Seizures, not hippocampal neuronal death, provoke neurogenesis in a mouse rapid electrical amygdala kindling model of seizures. Neuroscience in press.

Turnley, A.M. (2005). Role of SOCS2 in Growth Hormone Actions. Trends Endocrinol. Metab . 16, 53-58.

Turnley, A.M. (2005). Growth hormone and SOCS2 regulation of neuronal differentiation: possible role in mental function. Ped. Endocrinol. Rev. 2, 366-371.

Shen, P.-J., Yuan, C.-G., Ma, J., Cheng, S., Yao , M., Turnley, A.M. and Gundlach, A.L. (2005). Galanin in neuro(glio)genesis: Expression of galanin and receptors by progenitor cells in vivo and in vitro and effects of galanin on neurosphere proliferation. Neuropeptides. 39, 201-205.

Ransome, M.I. and Turnley, A.M. (2005). Analysis of cortical neuron subpopulations in mice over-expressing SOCS2. Neuroscience 132, 673-687.

Smith, P.D., McLean, K.J., Murphy, M.A., Wilson , Y., Murphy, M., Turnley, A.M. and Cook, M.J. (2005). A brightness-area-product based protocol for the quantitative assessment of antigen abundance in fluorescent immunohistochemistry. Brain Research Protocols 15, 21-29.

Wong. G.S.H., Goldshmit Y., and Turnley, A.M. (2004). IFN g but not TNF a promotes neuronal differentiation of neural stem cells. Exp. Neurol. 187, 171-177.

Goldshmit, Y., Walters, C.E., Scott, H.J., Greenhalgh, C.J. and Turnley, A.M. (2004). SOCS2 induces neurite outgrowth by regulation of EGF receptor activation. J. Biol. Chem. 279, 16349-16355.

Ransome, M.I., Goldshmit, Y., Bartlett , P.F., Waters, M.J. and Turnley, A.M. (2004). Comparative analysis of CNS populations in knockout mice with alterations in GH responsiveness. Eur. J. Neurosci. 19, 2069-2079 .

Goldshmit, Y., Greenhalgh, C.J. and Turnley, A.M. (2004). Suppressor of cytokine signaling-2 and epidermal growth factor regulate neurite outgrowth of cortical neurons. Eur. J. Neurosci. 20, 2260-2266 .

Goldshmit, Y., Galea, M.P., Wise, G., Bartlett , P.F. and Turnley, A.M. (2004). Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J. Neurosci. 24, 10064-10073.

Turnley, A.M., Faux, C.H., Rietze, R.L. Coonan, J.R., and Bartlett , P.F. (2002). Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling. Nature Neurosci. 5,1155-1162.