marbioEN

Dr. Smadar Ben Tabou de Leon

Smadar

Tel - Inside Univ: 8555

Tel - Out of Univ: +972-4-8288555

Room: 131, Multipurpose Building

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Laboratory: Gene Regulation in Development and Evolution, Room: 132, Multipurpose Building

 

Research Interests

Networks of regulatory genes control the differential expression of regulatory and structural genes and by that initiate and control the development of the body plan. Evolutionary changes of the functional organization of developmental gene regulatory networks are therefore the key molecular mechanism underlying evolutionary change of animal morphology. However, the relation between gene regulatory networks and the developmental tasks they execute is not always apparent: How do gene regulatory networks control complex developmental processes? How do changes in the regulatory circuitry translate into morphological changes and how do they lead to evolutionary innovations in the body plan? These questions lay at the most fundamental level of our understanding of developmental processes and their evolution. I address these questions by studying regulatory circuits that control specification, differentiation and morphogenesis in the sea urchin embryo and comparing them to regulatory circuits that control similar processes in the zebrafish embryo. In my work I combine novel high-through put experimental techniques with mathematical modeling, to further our understanding of the dynamic molecular control of developmental processes and their evolution.

 

Background: Sea Urchin and Zebrafish as model organisms for development and evolution

sea urchin copy The sea urchin is one of the classic model systems of development, with many characteristics that make it an excellent system for the molecular age. The ability to perform discrete perturbation assays and quantitative expression experiments enable the construction of one of the most elaborate models of the gene regulatory networks for animal development.

 

 

 

 

zebrafish The zebrafish is an emerging powerful model system for vertebrate development and disease. The external fertilization and the transparent embryos make early developmental stages accessible for experimental studies. Cutting edge imaging techniques allow unprecedented reconstruction of cell lineages which is a necessary step in studying developmental cellular transitions. Advanced genetic techniques available in zebrafish lead to novel understanding of developmental phenomena. I will use the complementary information and experimental techniques of the sea urchin and the zebrafish to access a broad range of developmental questions. I will study related regulatory circuits in the sea urchin and the zebrafish ectoderm in order to answer two fundamental evolutionary questions: is the formation of ortholog organs driven by a conserved regulatory code? What changes of the regulatory code enable the formation of a novel organ? I will initially apply this approach to the study a regulatory circuit that controls the aboral ectoderm specification in the sea urchin embryo and compare it to the regulatory circuits that control limb formation in vertebrates, particularly, fin-bud formation in zebrafish.

 

Current Research Projects: Patterning of the sea urchin aboral ectoderm and the resemblence to limb bud patterning in vertebrates

prismThe abo ral ectoderm of the sea urchin differentiates into squamous epidermis-like cells that the mesodermal derived larval skeleton is extended into. The genes that encode transcription factors tbx2/3, irxa and dlx are co-expressed in a dynamic spatio-temporal pattern in the aboral ectoderm, downstream of the BMP pathway and other regulatory signals. When the expression of either tbx2/3, irxa or dlx is down-regulated the extension of the larval skeleton is decreased and the gut formation is delayed, indicating that these genes are upstream of signaling pathways that are required for skeleton extension and gut normal formation. Interestingly, orthologs of these three genes play a role in limb formation in vertebrates. Orthologs of the Dlx transcription factor are expressed during appendages development in the arthropod limb, fish fin buds, tetrapod limb buds, polychaete annelid parapodia, onychophoran lobopodia, and ascidian ampullae. Orthologs of the T-box transcription factors, Tbx2/3 and Tbx4/5 play a role in the limb bud formation in vertebrates and particularly in fin bud formation in fish. Orthologs of the Irx transcription factor play a role in mouse limb formation. Apparently, the ectodermal expression of these genes originated once in a common ancestor and has been used subsequently to pattern body wall outgrowths in a variety of organisms.The expression pattern of these three genes in the sea urchin aboral ectoderm and their necessity for mesoderm morphogenesis (larval skeleton) might indicate that the regulatory circuit that these genes form is ortholog of the regulatory circuit that pattern the ectoderm where appendages are formed in other organisms.

To gain insight into the developmental role and the evolution of the regulatory circuit that tbx2/3 ,irxa and dlx form, I will study the upstream regulation of these genes in the sea urchin embryo and compare it to the regulation of these genes in the fin bud of zebrafish embryos. To understand the developmental role of this regulatory circuit I will identify the downstream targets of this circuit and study how they contribute to the skeleton morphogenesis in sea urchin and to the fin bud formation in zebrafish. Identifying conserved and diverged targets would provide unprecedented understanding of the molecular changes that lead to evolutionary changes the body plan.

 

Current model of the gene regulatory circuit that specifies the aboral ectoderm of the sea urchin

ectoderm GRN

 

 

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