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Taube P. Rothman, Ph.D.

Senior Research Scientist

E-mail: tpr2@columbia.edu

The developmental potential of cells from the neural crest

picture In my laboratory, we study the development of the vertebrate peripheral nervous system. Our research is focused on the developmental potential of neural crest-derived precursor cells that give rise to the nervous system of the gut. We study the interactions that occur between these cells and extracellular matrix molecules and growth factors that are critical for the development of the two intrinsic nerve plexuses that control gut motility. The lethal spotted (ls/ls) mutant mouse, an animal in which the terminal portion of gut is congenitally aganglionic, is one of the models utilized for our studies. It has recently been shown that segmental aganglionosis in ls/ls mice results from a single point mutation in the edn3 gene which encodes the protein endothelin-3 (EDN-3).

Currently, experiments are being done to determine which cells in the normal murine bowel express EDN-3, and/or its receptor EDNRB: crest-derived cells, non-neuronal enteric cells including smooth muscle, or both. We also would like to know why the terminal colon is the sole portion of the bowel that is aganglionic in EDN-3 deficient mice. Our studies have shown that specific extracellular matrix molecules are over expressed in the ls/ls terminal colon and have revealed that at least two of these molecules accumulate in the path of colonizing crest-derived cells. We are determining the role of these gene products in normal and mutant enteric development. Several techniques are utilized to address our questions, in vivo and in vitro. These include immunocytochemistry, immunoselection of crest-derived cells, reverse transcriptase in combination with the competitive polymerase chain reaction (RT-cPCR), Northern analyses, in-situ-hybridization, etc.

Selected publications
Rothman, T.P., Le Douarin, N.M., Fontaine-Pˇrus, J.C. and Gershon, M.D. (1990) Developmental potential of neural crest-derived cells migrating from segments of developing quail bowel back-grafted into younger chick host embryos. Development, 109:411-423.

Pham, T.D., Gershon, M.D. and Rothman, T.P. (1991) Time of origin of neurons in the murine enteric nervous system: Sequence in relation to phenotype. J. Comp. Neurol., 314:789-798.

Rothman, T.P., Goldowitz, D. and Gershon, M.D. (1993) Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of ls/ls mice: analysis with aggregation and interspecies chimeras. Dev. Biol., 159:559-573.

Rothman, T.P., Chen, J., Howard, M.J., Costantini, F., Schuchardt, A., Pachnis, V. and Gershon, M.D. (1996) Increased expression of laminin-1 and collagen (IV) subunits in the aganglionic bowel of ls/ls but not c-ret-/- mice. Dev. Biol., 178:498-513.

Chalazonitis, A., Rothman, T.P., Chen, J., Vinson, E.N., MacLennan, A.J., and Gershon, M.D. (1998) Promotion of the development of enteric neurons and glia by neuropoietic cytokines: Interactions with neurotrophin-3. Dev. Biol., 198:343-365.

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Last modified on Sept 4, 2001