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Faculty Profile

Address:
701 West 168 Street
Room 1402
New York, NY 10032

Phone: 212-305-4753
Fax: 212-305-5484

Lab Website

vep1@columbia.edu

Education and Training
Ph.D. 1972 University of Cambridge, England

Affiliations
Department of Genetics & Development



Training Activities
Chair, Training program in Genetics & Development
MD/PhD Program
Integrated Program in Cellular, Molecular & Biophysical Studies

Virginia E. Papaioannou, PhD
Professor
of Genetics & Development

Research Summary
Genetic control of mammalian embryogenesis and organogenesis and the role of T-box genes.

Our laboratory is interested in the genetic control of early mammalian development, from the first cleavage of the fertilized zygote through implantation, gastrulation, and early organogenesis. We use a variety of approaches to study the determination of cell lineages and the interactions of the developing embryo with the maternal environment, taking advantage of both naturally occurring and experimentally induced mutations. The major strength of the laboratory is the combination of classic experimental embryology techniques with molecular biology and targeted mutagenesis.
The major project in the laboratory is the study of a recently discovered family of transcription factor genes, the T-box gene family. These genes share a conserved DNA-binding motif first found in the Brachyury locus. The genes are highly conserved in evolution and have been implicated in the control of mesoderm formation and in inductive interactions in the organogenesis of organs such as mammary gland, heart, lung, and limbs. Several mutations in human T-box genes have been shown to be responsible for developmental birth defects and by using targeted mutagenesis, we have produced mouse models for the human DiGeorge syndrome (Tbx1) and the ulnar mammary syndrome (Tbx3). In addition, we are investigating the role of Tbx6 in somite specification and the decision between neural and mesodermal fates, and the roles ofTbx2, Tbx3, and Tbx4 in heart, limb and eye development. Our interest is in understanding how these genes control cell fate and tissue specification decisions during early development.

Skeletal preparations from wild type and Tbx1 mutant embryos. The mutant embryo on the right has abnormalities in the pharyngeal arch-derived skeletal structures in the head. This mutant provides a mouse model of the human DiGeorge syndrome Green fluorescent protein (GFP) expression under the control of the Tbx6 gene. This is a “knock-in” of a histone-GFP fusion gene into the Tbx6 locus. The fluorescence is a readout of Tbx6 gene activity

Service Activities
Editor of the journal Development

Selected Publications

1. Hadjantonakis, A. –K. and Papaioannou, V. E. 2004. Dynamic in vivo imaging and cell tracking using a histone fluorescent protein fusion in mice. BMC Biotechnology 2004, 4:33

2. Harrelson, Z., Kelly, R. G., Goldin, S. N., Bollag, R. J., Silver, L. M. and Papaioannou, V. E. 2004. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development 131:5041-5052

3. Kelly, R. G., Jerome-Majewska, L. A. and Papaioannou, V. E. 2004. Regulation of branchiomeric myogenesis by the del22q11.2 candidate gene Tbx1. Human Molecular Genetics 13:2829-2840.

4. Papaioannou, V. E. and Behringer, R. R. 2004.  Mouse Phenotypes, A Handbook of Mutation Analysis. Cold Spring Harbor Press, 235 pp.

5. Jerome-Majewska, L. A., Jenkins, G. P., Ernstoff, E., Zindy, F., Sherr, C. J. and Papaioannou, V. E. 2005.  Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Developmental Dynamics 234:922-933.

6. Naiche, L. A., Harrelson, Z., Kelly, R. and Papaioannou, V. E. 2005.  T-box genes in vertebrate development. Annual Review of Genetics 39:219-239. 116.


Current Projects

1. Predoctoral training grant in genetics and development
The Training Program in Genetics and Development is a vigorous predoctoral training program designed to train young scientists for productive research careers. The goals are 1) to provide a solid and broad education in genetics, including molecular genetics, developmental genetics, and human genetics; and 2) to provide rigorous training in biomedical research. The program emphasizes experimental skills and critical thinking. Trainees are drawn from all parts of the United States and around the world and usually have a BA or BS degree. Research areas include the regulation of gene expression and growth control in eukaryotic cells, the molecular genetics of cell differentiation and development, the genetics and pathogenesis of inherited disease, the molecular genetics of cancer, animal models for human genetic disease, human gene therapy, the genetics of recombination and linkage analysis. Another major strength of the program is the stimulating research environment in New York City and at the Health Sciences Campus of Columbia University. The research community encompasses many interactive departments and research institutes. Participation in the larger national and international scientific community thrives through the many excellent seminar series on campus. Core equipment and services are available, there is an outstanding biomedical library, and computer services and animal facilities are excellent.
National Institute of General Medical Sciences
7/1975-6/2006

2. Role of T-box Genes in Mouse Development
The long-term objectives of this project are to understand the evolution of the T-box family of transcription factor genes, to determine their role in embryonic development., and to understand interrelationships between the genes in terms of the evolution of developmental mechanisms. In this proposal, we focus on the Tbx2 subfamily, Tbx2, Tbx3, Tbx4, and Tbx5 because of their expression in the allantois, a new structure in evolutionary terms, and their potential role in the evolution and development of paired appendages of tetrapods. The Specific Aims will not only shed light on the genetic control of human development but also provide insight into the evolution of function within gene families. Specific Aim 1. Produce a multipurpose allele of Tbx5 to ablate gene function, allow real-time expression reporting and provide an allele that can be retargeted. Specific Aim 2. Produce a conditional allele of Tbx4 to study gene function late in development. Specific Aim 3. Investigate regulatory and genetic interactions between the genes of the Tbx subfamily, Tbx2, Tbx3, Tbx4, and Tbx5.
National Institute of Child Health and Human Development
2/1996-12/2006

3. Role of TBX6 in mesoderm patterning and somite formation
The objectives of this research are to understand the genetic control of mesoderm specification at gastrulation and to determine how decisions are made at critical junctures between alternative developmental pathways. Specific Aim 1. To determine the lineage of all Tbx6expressing cells in order to characterize fully the phenotypic results of a null mutation in Tbx6 and to examine the developmental potential of Tbx6 null cells. Specific Aim 2.To explore the mechanism of action of Tbx6 in the specification of mesoderm during gastrulation using a Cremediated transgenic approach for misexpression of Tbx6. Specific Aim 3. To produce a new Tbx6 mutant allele coding for a truncated protein with only the DNA binding domain and no transcriptional regulatory domain. Specific Aim 4. To isolate and characterize additional members of the Tbx6 subfamily in the mouse with special emphasis on isolating the orthologs of genes known in other species to play a role in mesoderm development.
National Institute of General Medical Sciences
7/2000-6/2004

Committee, Council Professional Society Memberships
American Society for Cell Biology
International Society for Differentiation
Society for Developmental Biology
American Association of Arts and Sciences

Editorial Boards
Molecular Reproduction and Development
Developmental Dynamics
Differentiation

Officer of the Harvey Society

Keywords
mouse, development, T-box, Tbx, targeted mutagenesis


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