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Gerald H. Thomsen, Ph.D.
Department of Biochemistry and Cell Biology
Life Sciences Building
Stony Brook University
Stony Brook, NY 11794-5215
Office telephone: 631-632-8536
- Research Description
Research in my lab seeks to understand the basic principles of how embryos develop by working on molecular mechanisms that drive a fertilized egg to form the many diverse cell types found in an embryo, and organize these cells into tissues and organs. Our prime focus is on vertebrate development, and we use two species of frogs, Xenopus laevis and Xenopus tropicalis, to discover and test the mechanism of regulatory genes governing early development. Current pursuits in this context include mechanisms of growth factor signaling in the TGFß superfamily, the function of ubiquitin ligases in signaling and cell differentiation, and the function of transcription factors (e.g. T-box genes) or transcriptional adaptor proteins. We are also studying the mechanisms of embryonic development in the sea anemone, Nematostella vectensis, a member of the ancient animal phylum Cnidaria, to gain insight into the evolution of animal developmental mechanisms and the origins of growth factor signaling systems.
Understanding the molecular basis of embryonic development is of basic importance, in and of itself, but this pursuit is also key to understanding mechanisms that underlie disease and birth defects in humans. Many of the regulatory mechanisms that govern embryonic development are similar if not identical to those that control the normal function of adult cells and tissues. Furthermore, many advances in biotechnology are fueled by new methods that stem from the study of embryonic development (e.g. the recent rise of RNAi through studies of C. elegans). Closer to our interests, the study of frog embryos (by many groups) has led to discovery and insight into the function of developmental regulators that have made their way into clinical testing, such as BMP, FGF and Wnt growth factors and their various inhibitors.
Our primary emphasis in studying Xenopus embryonic development is to understand how cell differentiation and pattern formation are regulated by cell-to-cell, or inductive signaling. Broad focus is on the roles played in early development by the two principal branches of TGFß signaling: the Vg1/nodal/activin pathway, and the BMP pathway. Present efforts seek to identify and understand the biochemical and embryonic functions of modulators of TGFß signal transduction, such as Smad-interacting factors, including ubiquitin ligases such as the Smurf1, which we discovered, and its relative Smurf2. We also are interested in the more general question of how ubiquitin-mediated protein degradation regulates early development by testing the embryonic function of ubiquitin ligases and their targets. Our basic experimental approach in all these studies is to test how gain and loss of gene function influences frog embryo development. We identify candidates genes by our own protein-protein interaction (PPI) screens, or PPI screens from systems biology databases. We also screen for candidates by functional assays in frog embryos, by differential gene expression information, or by homology with developmental or cell biological regulatory genes identified in other animals.
Sea Anemone Development
While Xenopus has been the traditional study organism in the lab, our studies have recently expanded to include the sea anemone Nematostella vectensis. Sea anemones belong to the phylum Cnidaria, which also includes corals, jellyfish and hydroids (e.g. Hydra). We are interested in sea anemones because they represent an ancient animal group that is considered “basal” to all other animals, except sponges and ctenophores. The last time cnidarians and vertebrates shared a common ancestor was about 650-700 million years ago. Therefore, by comparing the developmental programs of frog and sea anemone embryos we will gain new insights into the evolution and deployment of genetic and biochemical pathways that govern development. To date, studies on sea anemones have been mostly descriptive, but we and our collaborators (M. Martindale and A. Wikramanyake) are attempting to develop gain and loss of function methods by which to study sea anemone embryonic mechanisms. Furthermore, sea anemones can regenerate any part of their body, a process normally used for asexual reproduction. We are beginning to explore the molecular basis of this process, including the function of stem cells in adult anemones.
Iwasaki Y and Thomsen GH. (2014). The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling. Development (published Sept 10, 2014). PMID: 25209246. [ download PDF]
Kirmizitas A, Gillis WQ, Zhu H and Thomsen GH. (2014). Gtpbp2 is required for BMP signaling and mesoderm patterning in Xenopus embryos. Developmental Biology 392:358-367. PMID: 24858484 [ download PDF]
Nakayama T, Fish MB, Fisher M, Oomen-Hajagos J, Thomsen GH and Grainger RM. (2013). Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis. Genesis 51:835-843. PMID: 24123613 [ download PDF] Featured journal cover photo
Bossert PE, Dunn MP and Thomsen GH. (2013). A staging system for the regeneration of a polyp from the aboral physa of the Anthozoan Cnidarian Nematostella vectensis. (2013) Developmental Dynamics 242:1320-1321. PMID: 23913838 [ download PDF] Featured journal cover photo.
Sorrentino GM, Gillis WQ, Oomen-Hajagos J and Thomsen GH (2012). Conservation and evolutionary divergence in the activity of receptor-regulated smads. EvoDevo 3:22 [ download PDF] PMID 23020873
Callery, EM, Park, CY, Xu X, Zhu H, Smith JC and Thomsen GH. (2012). The endocytosis factor EPS15R is required for BMP signaling and differentially compartmentalizes with Smad proteins. Open Biology 2:120060 [ download PDF] PMID 22724065
Gersch R, Kirmizitas A, Sobkow L, Sorrentino G, Thomsen, GH, and Hadjiargyrou, M. (2012) Mustn1 expression is essential for craniofacial chondrogenesis during Xenopus development. Gene Expression Patterns. Published online 18 January 2012. 12:145-153. PMID 22281807, PMCID PMC3348343 [ download PDF]
Thomsen GH. (2012) Smurf1. UCSD Molecule Pages 1:31-43. [ download PDF]
Callery EM, Thomsen GH and Smith JC. (2010). A divergent Tbx6-related gene and Tbx6 are both required for neural crest and intermediate mesoderm development in Xenopus. Developmental Biology 340:75-87. PMID 20083100. [ download PDF]
Kalkan T, Iwasaki, Y, Park CY and Thomsen GH. (2009). Tumor necrosis factor-receptor-associated factor-4 is a positive regulator of TGF-beta signaling that affects neural crest formation. Molecular Biology of the Cell 20:3436-3450. [ download PDF]
Osmundson, EC, Ray D, Moore FE, Gao Q, Thomsen GH and Hiroaki Kiyokawa. (2008). The HECT-domain E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint and mitotic progression. Journal of Cell Biology 183:267-277. [ download PDF]
Matus D, Magie C, Martindale MQ and Thomsen GH. (2008). The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution. Developmental Biology 313:501-518. [ download PDF]
Matus DQ, Thomsen GH and Martindale MQ. (2007). FGF signaling in gastrulation and neural development in Nematostella vectensis, an anthozoan cnidarian. Development, Genes and Evolution. 217:137-148.. [ download PDF]
Alexandrova E. and Thomsen GH (2006). Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. Developmental Biology 299:398-410. [ download PDF]
Matus, DQ, Pang K, Marlow H, Dunn CW, Thomsen GH and Martindale, M.Q. (2006) Molecular evidence for deep evolutionary roots of bilaterality in animal development. Proceedings of the National Academy of Sciences 103:11195-11200. [ download PDF]
D.Q. Matus, G.H. Thomsen and M.Q. Martindale (2006). Evolutionarily conserved "dorso-ventral" genes are asymmetrically expressed and involved in germ layer demarcation during cnidarian gastrulation. Current Biology 17:499-505. [ download PDF]
G.H. Thomsen (2006). A new century of amphibian developmental Biology. Seminars in Cell and Developmental Biology 17:78-79. Note: This issue highlights Xenopus research and was edited by G.H. Thomsen (see below). [ download PDF]
E.M. Callery, J.C. Smith, and G.H. Thomsen (2005). The ARID domain protein XDril is required for TGFß signaling in Xenopus. Developmental Biology 278:542-559. [ download PDF]
H. Wang H., Y Zhang, A. Ogunjimi, E. Alexandrova, G.H. Thomsen and J.L. Wrana (2003). Regulation of Cell Polarity and Protrusion Formation by Targeting RhoA for Degradation. Science 302:1175-1179. [ download PDF]
P. Kavsak, R.K. Rasmussen, C.G. Causing,, S. Bonni, H, Zhu, G.H. Thomsen and J.L. Wrana (2000). Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGFb receptor for degradation. Molecular Cell 6:1365-1375.
P. Hoodless, T. Tsukazaki, S. Nishimatsu, L. Attisano, J. Wrana and G.H. Thomsen. (1999). Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and disrupt axis formation in Xenopus. Developmental Biology 207: 364-379.[ download PDF]
M. E. Horb and G.H. Thomsen. (1999). Tbx5 is essential for vertebrate heart formation. Development 126: 1739-1751.
H. Zhu, S. Abdollah, P. Kavsak, J. Wrana and G.H. Thomsen. (1999). A Smad ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400: 687-692. [ download PDF]
W. D. Tracey, M.E. Pepling, M.E. Horb, G.H. Thomsen and J.P. Gergen. (1998). A Xenopus homologue of AML-1 reveals unexpected patterning mechanisms leading to the formation of embryonic blood. Development 125: 1371-1380. [ download PDF]
S. Nishimatsu and G.H. Thomsen. (1998). Ventral mesoderm induction and patterning by BMP heterodimers in Xenopus embryos. Mechanisms of Development 74: 75-88. [ download PDF]
J. Tian, H. Gong, G.H. Thomsen and W. J. Lennarz. (1997) Xenopus laevis gamete interactions: Identification of sperm binding proteins in the egg vitelline envelope. Journal of Cell Biology 136: 1099-1108. [ download PDF]
M.E. Horb and G.H. Thomsen. (1997). A vegetally localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation. Development 124: 1689-1698.
J. Tian, H. Gong, G.H. Thomsen and W.J. Lennarz. (1997). Xenopus laevis sperm-Egg adhesion is regulated by modifications in the sperm receptor and vitelline envelope. Developmental Biology 187: 143-153. [ download PDF]
J. Tian, G.H. Thomsen, H. Gong and W.J. Lennarz. (1997). Xenopus Cdc6 confers sperm binding competence to mature oocytes in the absence of meiotic maturation. Proceedings of the National Academy of Sciences, USA 94:10729-10734. [ download PDF]
G.H. Thomsen. (1997). Antagonism within and around the Spemann organizer: BMP inhibitors in vertebrate body patterning. Trends in Genetics 13: 209-211. [ download PDF]
S. Nishimatsu, G.H. Thomsen and T. Nohno. (1997). Bone morphogenetic proteins and the body plan. Experimental Medicine (Japan) 15: 169-175.
G.H. Thomsen. (1996). Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor. Development 122: 2359-2366.
K. Eppert, S. W. Scherer, H. Ozcelik, R. Pirone, P. Hoodless, H. Kim, L. Tsui, B. Bapat, S. Gallinger, I. Andrulis, G.H. Thomsen, J. L. Wrana and L. Attisano. (1996). MADR2 maps to 18q21 and encodes a TGFß regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 86: 543-552.
Developmental Biology 203: 159-163. A. Hemmati-Brivanlou and G.H. Thomsen. (1995). Ventral mesodermal patterning in Xenopus embryos: The expression patterns and activities of BMP-2 and BMP-4. Developmental Genetics 17: 78-89.
P.D. Vize and G.H. Thomsen. (1994). Vg1 and regional specification in vertebrates: a new role for an old molecule. Trends in Genetics 10: 371-376. C. Dohrman, A. Hemmati-Brivanlou, G.H. Thomsen, A. Fields, T. Wolff, and D. Melton. (1993). Expression of activin mRNA during early development in Xenopus laevis. Developmental Biology157: 474-483.
G.H. Thomsen and D. A. Melton. (1993). Processed Vg1 protein is an axial mesoderm inducer in Xenopus. Cell 74: 433-441.
I. Harris, L. Mizrahi, T. Ziv, G.H. Thomsen and E. Mitrani. (1993). Identification of TGFß-related genes in the early chick embryo. Roux's Archives of
K. Wharton, G.H. Thomsen and W. Gelbart. (1991). Drosophila 60A gene, a new TGF-ß family member, is closely related to human bone morphogenetic proteins. Proceedings of the National Academy of Sciences, USA 88: 9214-9218.
G. H. Thomsen, T. Woolf, M. Whitman, S. Sokol, J. Vaughn, W. Vale and D. Melton. (1990). Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures. Cell 63: 4854.
E. Mitrani, K. Ziv, G. H. Thomsen, Y. Shimoni, D. A. Melton and A. Bril. (1990). Activin can induce the formation of axial structures and is expressed in the hypoblast of the chick. Cell 63: 495-501.
Guest Journal Editor
G.H. Thomsen (2006). Issue Editor: "Frog Embryo Development." Seminars in Cell and Developmental Biology 17:78-153.