Miles L. Epstein

 

 

Regulation of Neuronal Differentiation and Neurotransmitter Phenotype

E-mail: mepstein@wisc.edu

Research Strengths: Development: Plasticity and Repair, Molecular Neuroscience

After entering the gut, neural crest cells migrate, proliferate, and differentiate to form the intrinsic neurons of the gut. These neurons are located in ganglia along the length of the gut. Within a single ganglion, neurons of different transmitter phenotypes are found. These neurons form a network that controls the motor behavior of the gut. Thus, enteric neuronal circuitry is generated that processes intrinsic sensory information and produces a motor output, independent of the CNS.

Our interest is in elucidating the arrangement of the neurons in the enteric neuronal circuitry and mechanisms involved in the formation of this circuitry. Formation of the circuitry involves understanding what triggers the differentiation of precursor cells into neurons, what determines the type of transmitter synthesized, and what controls the neuron's finding the correct postsynaptic target. Growth factors play a major role in these processes. We are interested in determining both the location in the gut and the transmitter phenotype of daughters of a single progenitor cell. Our in vitro studies involve culturing neural crest-derived precursors to determine the role of the microenvironment on transmitter differentiation.

Selected Publications:

• Druckenbrod, N.R. and M.L. Epstein. 2005. The pattern of neural crest advance in the cecum and colon. Dev. Biol. 287: 125-133.
• Conner, P.J, P.J. Focke, D.M. Noden ,and M.L. Epstein. 2003. Appearance of Neurons and Glia with respect to the wavefront during colonization of the avian gut by neural crest cells. Dev. Dynamics 226: 91-98.
• Focke, P.J., A.R. Swetlik, J.L. Schiltz, and M.L.Epstein. 2003. GDNF and insulin cooperate to enhance the proliferation and differentiation of enteric crest-derived cells. J. Neurobiology 55: 151-164.
• Focke, P.J., C.A. Schiltz, S.E. Jones, J.J. Watters, and M.L. Epstein. 2001. Enteric neuroblasts require the phosphatidylinositol 3- kinase pathway for GDNF-stimulated proliferation. J. Neurobiol. 47: 306-317. [PDF]
• Schiltz, C.A., J. Benjamin, and M.L. Epstein. 1999. The expression of the GDNF receptors Ret and GFRa1 in the developing avian enteric nervous system. J. Comp. Neurol. 414: 193-211. [PDF]
• Peters, R.J., M.A. Osinski, J.A. Hongo, G.A. Bennett, A.J. Okragly, M. Haak-Frendscho, and M.L. Epstein. 1998. Glial Derived Growth Factor (GDNF) is abundant in the adult rat gut. J. Autonomic Nervous Syst. 70: 115-122.