Daniel S. Kessler, Ph.D.
3400 Civic Center Boulevard
Philadelphia, PA 19104-6058
Cornell University, 1986.
Ph.D. (Molecular Biology)
Rockefeller University, 1990.
Description of Research ExpertiseResearch 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.
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.
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.
Lisa Chang, Thesis Student
Michelle Chen, High School Student
Lilun Li, Undergraduate Assistant
Liliam Pineda-Salgado, Postdoctoral Fellow
Christine Reid, Thesis Student
Selected PublicationsReid Christine D, Steiner Aaron B, Yaklichkin Sergey, Lu Qun, Wang Shouwen, Hennessy Morgan, Kessler Daniel S: FoxH1 mediates a Grg4 and Smad2 dependent transcriptional switch in Nodal signaling during Xenopus mesoderm development. Developmental biology 414(1): 34-44, Jun 2016.
Reid Christine D, Zhang Yan, Sheets Michael D, Kessler Daniel S: Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer. Developmental biology 368(2): 231-41, Aug 2012.
Bae Sangwoo, Reid Christine D, Kessler Daniel S: Siamois and Twin are redundant and essential in formation of the Spemann organizer. Developmental biology 352(2): 367-81, Apr 2011.
Chang Lisa L, Kessler Daniel S: Foxd3 is an essential Nodal-dependent regulator of zebrafish dorsal mesoderm development. Developmental biology 342(1): 39-50, Jun 2010.
Blythe, S.A., Reid, C.D., Kessler, D.S., and P.S. Klein: Chromatin immunoprecipitation in early Xenopus laevis embryos. Developmental Dynamics 238: 1422-1432, 2009.
Yaklichkin, Sergey. Steiner, Aaron B. Lu, Qun. Kessler, Daniel S.: FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus. Journal of Biological Chemistry 282: 2548-2557, 2007.
Yaklichkin S. Vekker A. Stayrook S. Lewis M. Kessler DS.: Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators. BMC Genomics 8: 201, 2007.
Steiner, Aaron B. Engleka, Mark J. Lu, Qun. Piwarzyk, Eileen C. Yaklichkin, Sergey. Lefebvre, Julie L. Walters, James W. Pineda-Salgado, Liliam. Labosky, Patricia A. Kessler, Daniel S.: FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development. Development 133: 4827-4838, 2006.
O’Hara, F.P., Beck, E., Barr, L.K., Wong, L., Kessler, D.S.* and R.D. Riddle *corresponding author: Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development 132: 3163-3173, 2005.
Pineda-Salgado, L., Craig, E.J., Blank, R.B. and D.S. Kessler: Expression of Panza, an alpha-2-macroglobulin, in a restricted dorsal domain of the primitive gut in Xenopus laevis. Gene Expression Patterns 6: 3-10, 2005.