SCOTT T. DOUGAN
Assistant Professor
Ph.D. 1995
The Rockefeller University, New York
RESEARCH
We study vertebrate development, focusing on the mechanisms underlying the induction and patterning of the three germ layers, and the coordinated interaction cells from distinct germ layers to form functional organs. In humans, disrupting these processes results in aberrant cell behavior and can lead to birth defects such as holoprosencephaly as well as diseases such as cancer. Therefore, elucidating the molecular, genetic and cellular mechanisms of normal development may lead to advances in the early diagnosis, treatment and prevention of human disorders.
The zebrafish, Danio rerio, is an ideal model system in which to study these questions because the embryos are transparent and develop rapidly outside the body of the mother, facilitating analysis of developmental processes in live embryos at single cell resolution. Furthermore, systematic large-scale mutant screens have identified numerous genes required for gastrulation and organogenesis.
We are also investigating how the response to Nodal signals is regulated throughout development. For example, cells require different levels of Nodal signals depending on their position along the dorsoventral axis (Dougan et al, submitted). Differential regulation of the squint and cyclops genes in dorsal and ventrolateral cells contributes to these different sensitivities to nodal gene dosage. Therefore, we are currently investigating the regulatory control regions of these two genes with the aim of identifying the pathways that control their expression at different stages of development. These studies will also generate tools for examining how cells generate distinct responses to Nodal signals at different times.
Our previous work implicated Squint and Cyclops, two closely related secreted proteins of the nodal-related subclass of the TGF-b superfamily, in the induction and patterning of mesoderm and endoderm in zebrafish (see figure). Although squint and cyclops have overlapping functions in the formation of mesoderm and endoderm, each gene also has unique requirements. Evidence from other labs suggests that the two proteins may have distinct biochemical activities that may explain these different requirements. For example, the Squint ligand acts directly on cells at a distance, like a morphogen, while Cyclops acts only over short distances (Chen and Schier, 2001). Nonetheless, many sqt single mutants survive to adulthood utilizing only cyclops function (Dougan et al., submitted). We are currently investigating the in vivo activities of these two proteins in order to determine how the short-ranged signal, Cyclops, can compensate for the loss of the Squint morphogen.
Photographs of live wild-type and mutant zebrafish embryos at 24 h post-fertilization
| CONTACT INFORMATION |
| (706) 583-8194, dougan@cb.uga.edu Xiang Fan, Postdoc: (706) 583-8191 |
| SEE ALSO |
| ZFIN Talbot Lab Georgia Cancer Coalition Biomedical & Health Sciences Institute |
OF NOTE
SUPPORT STAFF
 |
|
 |
| Fan | |
Webster |
| NAME |
|
POSITION | |
E-MAIL |
|
||||
| Xiang Fan | |
Postdoc | |
fan_xiang@hotmail.com |
|
||||
| Tina Sias | |
Research Tech III | |
csias@uga.edu |
|
||||
| Danielle Webster | |
Grad Student | |
dwebster@uga.edu |
|
||||
REPRESENTATIVE PUBLICATIONS
Dougan, S.T., R. M. Warga, D. O. Kane, A. F. Schier, and W.S. Talbot.2003 "The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm." Development 130(9):1837-1851.Wehrli, M.*, S.T. Dougan*, K. Caldwell, L. O'Keefe, S. Schwartz, D. Vaizel-Ohayon, E. Schejter, A. Tomlinson, S. DiNardo. 2000. "Arrow encodes an LDL receptor related protein essential for Wingless signaling in Drosophila." Nature 407: 527-530. *joint first authors
Sirotkin, H.I., S.T. Dougan, A.F. Schier, and W.S. Talbot. 2000. "Bozozok and squint act in parallel to specify dorsal mesoderm and anterior neuroectoderm in zebrafish." Development 127: 2583-2592.
Feldman, B., S.T. Dougan, A.F. Schier, and W.S. Talbot. 2000. "Nodal-related signals establish mesendodermal fate and trunk neural identity in zebrafish." Current Biology 10: 531-534.
Gates, M.A., L. Kim, E.S. Egan, T. Cardozo, H.I. Sirotkin, S.T. Dougan, D. Lashkari, R. Abagyan, A.F. Schier, and W.S. Talbot. 1999. "A genetic linkage map for zebrafish: Comparative analysis and localization of genes and expressed sequences." Genome Research 9: 334-347.
Feldman, B., M.A. Gates*, E. S. Egan*, S.T. Dougan*, G. Rennebeck*, H.I. Sirotkin, A.F. Schier and W.S. Talbot. 1998. "Zebrafish organizer development and germ-layer formation require nodal-related signals." Nature 395: 181-185. *joint first authors
O'Keefe, L., S.T. Dougan, L. Gabay, E. Raz, B-Z. Shilo, and S. DiNardo. 1997. "Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis." Development 124: 4837-4845
DiNardo, S., J. Heemskerk, S.T. Dougan, and P. O'Farrell. 1994. "The making of a maggott: patterning the Drosophila embryonic epidermis." Current Opinion in Genetics and Development 4: 529-534.
Dougan, S., and S. DiNardo. 1992. "Drosophila wingless generates cell type diversity among engrailed expressing cells." Nature 360: 347-350.
Sheng, M.S., S.T. Dougan, G. McFadden, and M.E. Greenberg. 1988. "Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences." Mol. Cell. Biol. 8(7): 2787-2796.