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.
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.
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