Alcmène Chalazonitis, Ph.D.
Senior Research Scientist
When I joined this department 12 years ago, I became fascinated with the development of the enteric nervous system (ENS). My previous research pertained to studies of the development of the peripheral nervous system (specifically sympathetic and sensory neurons) and included elucidating the biological actions of several trophic factors important in the development and physiology of the PNS. Taking advantage of the intellectual environment I found collaborating with Michael Gershon, Taube Rothman and others, I have focused on elucidating the molecular signals that play a role in the commitment, differentiation, survival and diversification of the enteric neuronal and glial precursors. More specifically, using both in vitro and in vivo approaches we have identified several neurotrophic factors, found within the developing rat and mouse gut, that play essential roles in development of the ENS. Moreover it has been of interest to find that these factors influence the development of the enteric neurons and glia in a sequential, rather than simultaneous fashion. The factors identified so far are: GDNF, NT-3, the neuropoietic cytokines CNTF and LIF and the soluble form of the alpha1 subunit of laminin –1.
Currently, we are elucidating the role of regulatory molecules present within the bowel that regulate the onset of responsiveness of the enteric neuronal and glial precursors to these neurotrophic factors at different stages of development .
Selected publicationsPomeranz, H.D., Rothman, T.P., Chalazonitis, A., Tennyson, V.T. and Gershon, M.D. Neural crest-derived cells isolated from the gut by immunoselection develop neuronal and glial phenotypes when cultured on laminin. Devel. Biol. 156:341-361, 1993.
Chalazonitis, A., Rothman, T.P., Chen, J., Lamballe, F., Barbacid, M. and Gershon, M.D. Neurotrophin-3 induces neural crest-derived cells from fetal rat gut to develop in vitro as neurons or glia. The J. Neurosci. 14:6571-6584, 1994.
Chalazonitis, A., Tennyson, V.M., Kibbey, M.C., Rothman, T.P., and Gershon, M.D. The alpha1 Subunit of Laminin-1 Promotes the Development of Neurons by Interacting with LBP110 Expressed by Neural Crest-Derived Cells Immunoselected from the Fetal Mouse Gut. J. Neurobiol. 33:118-138, 1997.
Chalazonitis, A., Rothman, T.P., Chen, J., Vinson, E.N., MaCLennan, A.J. and Gershon, M.D. Promotion of the Development of Enteric neurons and Glia by Neuropoietic Cytokines: Interactions with Neurotrophin-3. Devel. Biol. 198:343-365, 1998.
Chalazonitis, A., Rothman, T.P. Chen, J., and Gershon, M.D. Age-dependent Differences in the Effects of GDNF and NT-3 on the Development of Neurons and Glia from Neural-Crest-Derived Precursors Immunoselected from the Fetal Rat Gut: Expression of GFRalpha1 in vitro and in vivo. Devel. Biol. 204:385-406,1998.
Chalazonitis, A., Pham,T.D., Rothman T.P., DiStefano P.S., Bothwell M., Blair-Flynn J., Tessarollo, L. and Gershon M.D. Neurotrophin-3 is Required for the Survival-Differentiation of Subsets of Developing Enteric Neurons. The J. Neurosci. 21:5620-5636, 2001.
Gershon, M.D., Chalazonitis, A., and Rothman, T.P. Ontogeny of neurons and glia of the enteric nervous system: Sources and signals that shape development. Advances in the Innervation of the Gastrointestinal Tract. Proc. of the Intrnl Conf on Innerv. of the GI tract, Munich, 1992.
Gershon, M.D., Chalazonitis, A., and Rothman, T.P. From Neural Crest to Bowel: Development of the enteric nervous system. J. Neurobiol. 24(2) 199-214, 1993.
Chalazonitis, A., Neurotrophin-3 as an Essential Signal for the Developing Nervous System. Molecular Neurobiology. 12: 39-53, 1996.