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Cell and Molecular Biology Graduate Group


Daniel S. Kessler

Daniel S. Kessler
Associate Professor, Cell and Developmental Biology
Program Chair, Development Biology Program

Developmental, Stem Cell and Regenerative Biology Program


Address

office:

1110 Biomedical Rsch Bldg (BRB) II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058

Office tel.: 215 898-1478
Lab tel.: 215 898-8492
Fax: 215 573-7601
E-mail: kesslerd@mail.med.upenn.edu


Link(s)

Dan Kessler at the Cell and Dev Bio Dept

Education

Cornell University. B.S. (Biology/Genetics) 1986

Rockefeller University, Ph.D. (Molecular Biology), 1990

 

Research Interests

  • Establishment and organization of the primary germ layers
  • Formation and function of the Spemann organizer in axial development
  • Signaling and transcriptional networks in the vertebrate gastrula

Key words: development, embryo, germ layer, mesoderm, endoderm, organizer, differentiation, morphogenesis, Xenopus, zebrafish, transcription, corepressors, signal transduction, Nodal, TGFß, Wnt, Fox, homeobox.

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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 focus of our research with Xenopus and zebrafish embryos is the development of the primary germ layers that establish the major embryonic cell lineages, and the formation of the Spemann organizer, a specialized group of cells that organizes the body plan. We are using biochemical, molecular, genomic 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 inductive signal used to generate distinct cellular 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 the developmental functions of the Spemann organizer. In our studies of germ layer formation, we have focused on a TGFß-related inducer, Nodal, which is essential for both mesodermal and endodermal development, and have identified genes that regulate Nodal and the cellular response to Nodal. Ongoing projects address the role of VegT, an essential maternal T-box gene that activates Nodal transcription to induce mesoderm and endoderm. We are also studying Fast1, FoxD3, and Sox17, transcription factors that modulate the expression of Nodal genes and the cellular response to Nodal signals. 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.

Recent Publications

O'Hara, F.P., Beck, E., Barr, L.K., Wong, L., Kessler, D.S.* and R.D. Riddle. (2005). Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development 132: 3163-3173.
*Corresponding author

Pineda-Salgado, L., Craig, E.J., Blank, R.B. and D.S. Kessler. (2005). Expression of Panza, an alpha2-macroglobulin, in a restricted dorsal domain of the primitive gut in Xenopus laevis. Gene Expression Patterns 6: 3-10.

Steiner, A.B., Engleka, M.J., Lu, Q., Piwarzyk, E.C., Yaklichkin, S., Lefebvre, J.L., Walters, J.W., Pineda-Salgado, L., Labosky, P.A. and D.S. Kessler. (2006). FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal. Development 133: 4827-4838.

Yaklichkin, S., Steiner, A.B., Lu, Q. and D.S. Kessler. (2007). FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus. Journal of Biological Chemistry 282: 2548-2557.

Yaklichkin, S., Vekker, A., Stayrook, S., Lewis, M., and D.S. Kessler. (2007). Prevalence of the eh1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators. BMC Genomics 8: 201.

Lab

Rotation Projects

A range of projects relating to the induction of the primary germ layers, formation of the Spemann organizer, patterning of the body axis, and transcriptional networks of the gastrula are being pursued using biochemical, molecular, genomic and embryological approaches. Specific projects include:

  1. Transcriptional targets of FoxD3 in Nodal regulation and mesoderm induction.
  2. Mechanisms of Sox17 control of the endodermal response to Nodal signals.
  3. Regulation of TGFß signals and transcriptional targets by Groucho corepressors.
  4. Goosecoid repression of Wnt signaling in the Spemann organizer.
Lab personnel:
Lisa Chang, Thesis Student
Morgan Hennessey, Undergraduate Assistant
Qun Lu, Research Specialist
Allie Misner, Undergraduate Assistant
Liliam Pineda-Salgado, Postdoctoral Fellow
Christine Reid, Thesis Student
last updated 8/2007
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