Description of Research Expertise

Research Interests
Signal Transduction and Transcriptional Regulation in the Vertebrate Embryo

Key words: development, embryo, germ layer, xenopus, transcription, signal transduction, Wnt, TGF-beta, homeodomain, zebrafish, differentiation, morphogenesis.

Description of Research
The emergence of the vertebrate body plan from the fertilized egg is a consequence of numerous inductive, morphogenetic and differentiation events. In our lab, we study the signal transduction and transcriptional mechanisms that pattern the vertebrate embryo.



The homeodomain gene, Siamois, can mimic the activity of the Spemann organizer. Siamois misexpression in ventral mesoderm induced complete axial duplication and the ectopic axis contains notochord, somitic muscle, spinal cord and brain. The embryo was stained with an antibody to visualize neural tissues.

The primary focus of our research with the amphibian, Xenopus laevis, is the development of Spemann's organizer, a specialized group of cells that regulates formation of the body plan, and the development of the primary germ layers that form embryonic mesoderm and endoderm. We are using biochemical, molecular and embryological approaches to address two fundamental questions: 1) What are the transcriptional regulatory pathways that establish and refine pattern in the gastrula; and 2) How is an individual signal used to generate distinct responses during development?

In our studies of organizer formation we have identified a transcriptional cascade of activators and repressors that regulate organizer formation and function. Ongoing projects in this area include the analysis of Siamois, Twin, and Goosecoid, homeobox genes required for organizer formation and function. In our studies of germ layer formation, we have identified signals required for mesodermal and endodermal development and have identified genes that regulate the expression of and response to germ layer-inducing signals. Ongoing projects address the role of VegT, a maternal T-box gene, and Nodal-related members of the TGFbeta family, in mesodermal and endodermal development. We are also studying FoxD3 and Sox17, transcription factors that regulate the expression of Nodal genes and the cellular response to Nodal proteins, respectively. The ultimate goal of our work is to identify the critical genes and pathways that establish the major lineages and signaling centers of the vertebrate embryo.

Rotation Projects for 2006-2007

Siamois and Twin Projects:

1. The mechanisms of DNA-binding and transcriptional activation by Siamois and Twin;
2. The cooperation of Siamois and Twin with TGFbeta-induced transcription complexes in establishing organizer transcription;
3. The identification and analysis of organizer genes that are direct targets of Siamois and Twin; and
4. The isolation and analysis of Siamois/Twin orthologs from the zebrafish and mouse embryos.

Goosecoid Projects:

1. The interaction of Goosecoid with TGFbeta signals in regulating Xwnt8 transcription;
2. The role of multiple Goosecoid-binding sites in generated graded expression of Xwnt8; and
3. The mechanisms of transcriptional repression by Goosecoid, including the role of Groucho corepressor factors.

VegT and Nodal Projects:

1. Identification of maternal signals that activate Nodal expression in the endoderm;
2. Analysis of the cooperation of Nodal and VegT in endodermal development; and
3. Examination of the transcriptional regulation of endoderm-specific genes by Nodal and VegT.

FoxD3 Projects:

1. Analysis of the requirement for FoxD3 function in mesodermal development;
2. Examination of the interaction of FoxD3 with the Nodal signaling pathway;
3. The mechanisms of transcriptional repression by FoxD3 and Groucho corepressor; and
4. Identification of direct target genes of FoxD3.

Sox17 Projects:

1. Analysis of the interaction of Sox17 with the Nodal signaling pathway;
2. Analysis of the regulatory effects of Sox17 on the transcription of Nodal target genes; and
3. Identification and analysis of Sox17 target genes in the endoderm and mesoderm.

Lab personnel:
Lisa Chang, Thesis Student
Virendra Desai, Undergraduate Assistant
Qin Lu, Research Specialist
Xiaotian Ming, Postdoctoral Fellow
Pat O'Hara, Research Specialist
Liliam Pineda-Salgado, Postdoctoral Fellow
Christine Reid, Thesis Student
Aaron Steiner, Thesis Student