Associate 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.

Photographs of live wild-type and mutant zebrafish embryos at 24 h post-fertilization

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.

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.

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

• 2001 Georgia Cancer Coalition Distinguished Cancer Clinician/Scientist

SUPPORT STAFF

Fan

NAME		POSITION		E-MAIL
Rebecca Ball		Reseach Tech III		rebbal55@uga.edu
Xiang Fan		Postdoc		fan_xiang@hotmail.com
Yuhua Sun		Postdoc		yhsun@uga.edu

REPRESENTATIVE PUBLICATIONS

X. Fan and S. T. Dougan (2007). The evolutionary origin of nodal-related genes in teleosts. Dev Genes Evol. 217 (11-12): 807-13.

Fan, X, E. G. Hagos, B. Xu, C. Sias, K. Kawakami, R. Burdine and S.T. Dougan(2007). Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish. Dev. Biol. 310 (2): 363-78.

Hagos, E. G., X. Fan and S.T. Dougan (2007). The role of maternal Activin-like signals in zebrafish embryos. Dev. Biol. 309 (2): 245-58.

Hagos, E.G and S.T. Dougan (2007). Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish. BMC Dev. Biol. 7(1): 22 Designated “Highly Accessed”—one of the journal’s top 10 most-viewed articles between March 2007-08; featured as “Image of the Month” for May, 2007.

Whipps, C. M, S. T. Dougan and Michael L. Kent (2007). Mycobacterium haemophilum infections of zebrafish (Danio rerio) in research facilities. FEMS Microbiol Lett. 270 (1): 21-26.

Dougan, S.T., R.M. Warga, D.A. 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: 1837-51. [Approximately 15% of the research for this publication was performed at UGA].

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