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The Journal of Neuroscience, November 26, 2008, 28(48):12622-12631; doi:10.1523/JNEUROSCI.0563-08.2008

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Development/Plasticity/Repair
Glutamatergic Neuronal Differentiation of Mouse Embryonic Stem Cells after Transient Expression of Neurogenin 1 and Treatment with BDNF and GDNF: In Vitro and In Vivo Studies

Jeannie H. Reyes,^1,2 K. Sue O'Shea,² Noel L. Wys,¹ J. Matthew Velkey,² Diane M. Prieskorn,¹ Karolina Wesolowski,¹ Josef M. Miller,¹ and Richard A. Altschuler^1,2

¹Kresge Hearing Research Institute, Department of Otolaryngology, and ²Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-0506

Correspondence should be addressed to Richard A. Altschuler, Kresge Hearing Research Institute, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5616. Email: shuler{at}umich.edu

Differentiation of the pluripotent neuroepithelium into neurons and glia is accomplished by the interaction of growth factors and cell-type restricted transcription factors. One approach to obtaining a particular neuronal phenotype is by recapitulating the expression of these factors in embryonic stem (ES) cells. Toward the eventual goal of auditory nerve replacement, the aim of the current investigation was to generate auditory nerve-like glutamatergic neurons from ES cells. Transient expression of Neurog1 promoted widespread neuronal differentiation in vitro; when supplemented with brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), 75% of ES cell-derived neurons attained a glutamatergic phenotype after 5 d in vitro. Mouse ES cells were also placed into deafened guinea pig cochleae and Neurog1 expression was induced for 48 h followed by 26 d of BDNF/GDNF infusion. In vivo differentiation resulted in 50–75% of ES cells bearing markers of early neurons, and a majority of these cells had a glutamatergic phenotype. This is the first study to report a high percentage of ES cell differentiation into a glutamatergic phenotype and sets the stage for cell replacement of auditory nerve.

Key words: stem cells; development; glutamate; auditory; cochlea; cell fate; neurogenesis; neuron

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Received Sept. 30, 2008; accepted Oct. 8, 2008.

Correspondence should be addressed to Richard A. Altschuler, Kresge Hearing Research Institute, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5616. Email: shuler{at}umich.edu

Related articles in J. Neurosci.:

Differentiation of Mouse Embryonic Stem Cells into Spiral Ganglion Neurons: A Therapeutic Approach to Deafness

Jennifer C. Boer, Karen E. Carney, and Sygrid van der Zee
J. Neurosci. 2009 29: 5711-5712. [Full Text]  

This article has been cited by other articles:

				J. C. Boer, K. E. Carney, and S. van der Zee Differentiation of Mouse Embryonic Stem Cells into Spiral Ganglion Neurons: A Therapeutic Approach to Deafness J. Neurosci., May 6, 2009; 29(18): 5711 - 5712. [Full Text] [PDF]

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