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Warren G. Tourtellotte, MD, PhDAssociate Professor
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Our lab studies the role of early growth response (Egr) genes, a family of transcriptional regulators that are important for nervous system development and adult nervous system function. As potential regulators of growth factor signaling, Egr proteins have an important role in cellular growth and differentiation, and they may behave as oncogenes in a variety of solid tumors. In the adult nervous system, Egr gene expression is regulated by synaptic activity and Egr proteins are important to regulate gene expression related to learning and memory processing. We are focusing on the mechanisms of Egr protein action in three main areas:
I. Regulation of muscle stretch receptor development. In work pioneered by our laboratory, we found that Egr3 is upregulated in a small number of muscle cells after they are innervated by sensory axons during muscle development. The sensory axon contacted myotubes are fate specified by Egr3 to become muscle spindle stretch receptors that are necessary for normal stretch reflexes and coordinated limb movements. We are currently using a variety of contemporary molecular-genetic techniques including microarray analysis, recombinant virus mediated gene transfer and transgenic mouse models to understand the repertoire of target genes regulated by Egr3 and its role stretch receptor fate specification.
II. Sympathetic nervous system development. The sympathetic nervous system is critical for organ and tissue homeostasis. Sympathetic neurons depend upon target tissue derived growth factors such as nerve growth factor (NGF) for survival during development. Egr genes are regulated in sympathetic neurons by NGF and other growth factor signaling and accordingly, Egr-gene deficient mice have prominent defects in sympathetic nervous system development. We are characterizing the role of Egr genes in sympathetic nervous system development using Egr gene deficient mice, novel transgenic reporter mice and microarray studies to characterize target genes regulated by Egr proteins.
III. Role in learning and memory processing. Egr transcription factors are regulated by synaptic activity and Egr1 is widely recognized to be involved in gene regulation required for learning and memory. We are characterizing the role of other Egr transcription factors in learning and memory using a variety of novel gain-of-function and conditional loss-of-function mutant mice and characterizing their behavior in learning and memory. We are examining the role of a variety of potential target genes regulated by Egr proteins in learning and memory.
Carter, J.H. and Tourtellotte, W.G. 2007. Early growth response transcriptional regulators are dispensable for macrophage differentiation. J Immunol 178(5): 3038-3047.
Li, L., Yun, S.H., Keblesh, J., Trommer, B.L., Xiong, H., Radulovic, J., and Tourtellotte, W.G. 2007. Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol Cell Neurosci 35(1): 76-88.
Carter, J.H., Lefebvre, J.M., Wiest, D.L., and Tourtellotte, W.G. 2007. Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival. J Immunol 178(11): 6796-6805.
L. Li, J. Carter, X. Gao, J. Whitehead and W.G. Tourtellotte (2005) The neuroplasticity-associated arc gene is a direct transcriptional target of early growth response (Egr) transcription factors. Mol. Cell. Biol. 25:10286-10300.
Y. Albert, J. Whitehead, L. Eldredge, J. Carter, X. Gao and W.G. Tourtellotte (2005) Transcriptional regulation of myotube fate specification and intrafusal muscle fiber morphogenesis. J. Cell. Biol. 169: 257-268.
J. Whitehead, C. Keller-Peck, J. Kucera and W.G. Tourtellotte (2005) Glial cell-line derived neurotrophic factor-dependent fusimotor neuron survival during development. Mech. Devel. 122: 27-41.
H-H. Chen, W.G. Tourtellotte and E. Frank (2002) Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons. J. Neurosci. 22: 3512-3519.
W.G. Tourtellotte, C. Keller-Peck, J. Milbrandt, J. Kucera (2001) The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis. Dev. Biol. 232: 388-399.
W.G. Tourtellotte, R. Nagarajan, A. Bartke and J. Milbrandt. (2000) Redundant Function of Egr1 and Egr4 in Murine Luteinizing Hormone Regulation and Leydig Cell Steroidogenesis. Mol. Cell. Biol. 20: 5261-5268
W.G. Tourtellotte, R. Nagarajan, A. Auyeung, C. Mueller and J. Milbrandt (1999) Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4 deficient mice. Devel. 126: 5061-5071.
W.G. Tourtellotte and J. Milbrandt. (1998) Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat. Genet. 20: 87-91.
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View Publications by Warren Tourtellotte listed in the National Library of Medicine (PubMed). |
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