Bradley Davidson

Assistant Professor of Molecular & Cellular Biology
Ph.D., University of Washington

We study heart development in the primitive chordate, Ciona intestinalis.  The simplicity of this organism allows us to decipher conserved transcriptional and cellular events underlying the earliest steps of heart formation.

Research Interests

In a vertebrate embryo, cells are first instructed to form heart by a complex array of signals from neighboring cells, including FGF8.  Complex interactions between these signals have made it difficult to tease out the specific contribution of individual factors. This problem is exacerbated by redundancy in these pathways. For example, there are four vertebrate FGF receptors with numerous isoforms and approximately 20 distinct FGF ligands. Furthermore, each of these factors coordinates multiple aspects of development; influencing cell behavior as well as regulatory gene expression. Deciphering how signaling factors direct discrete cell behaviors is challenging in the dense architecture of vertebrate embryos. In order to side-step some of these challenges we have initiated studies of heart development in the sea squirt, Ciona intestinalis.

Ciona is a chordate and thus a member of our own phyla. This close evolutionary relationship makes Ciona genetically more similar to humans than other invertebrate model systems. The single-chambered Ciona heart forms by similar processes as the vertebrate heart tube, but in the context of a highly simplified embryo. Ciona has only one copy of many key developmental genes that were later duplicated in the vertebrates, allowing stringent assessment of gene function. Additionally, low cell numbers permit unprecedented visualization of cell morphology and migration. Despite this simplicity, the fundamental program for early vertebrate heart development is conserved in Ciona.

Currently, our research is focused on revealing the precise function of FGF in early heart development. We have demonstrated that FGF signaling causes a group of 4 founder cells to undergo an asymmetric division. The smaller daughters of this division respond to continued FGF signaling by activating heart genes and migrating towards the site of future heart formation while the larger daughters form tail muscle. Through transgenic manipulations, we can disrupt FGF signaling specifically in these four cells, blocking heart development. Conversely, we can activate downstream factors and cause the entire group of cells to migrate and form extra heart tissue.

We have now begun to isolate Ciona heart cells and examine lineage-specific gene expression. This analysis employs micro-arrays designed to probe all predicted coding regions in the Ciona genome. This research has identified an extensive set of heart genes up-regulated by FGF. Future studies will focus on determining the role of these FGF target genes in heart development as well as identifying the precise transcriptional mechanisms by which FGF and downstream factors co-ordinate heart gene expression. We are particularly interested in the mechanisms by which FGF signaling generates an asymmetric division in the heart lineage. We are investigating the potential role of characterized cell polarity genes in this process and how they respond to FGF to shift the plane of heart cell division.

Select Publications

Any link on the below references will take you off of the BMCB site and to an abstract of that particular paper.

Davidson, B. 2007. Ciona intestinalis as a model for cardiac development. Seminars in Cell & Developmental Biology 18: 16-26.

Davidson, B., W. Shi, J. Beh, L. Christiaen, and M. Levine. 2006. FGF signaling delineates the cardiac progenitor field in the simple chordate, Ciona intestinalis. Genes & Development 20: 2728-2738.

Davidson, B., and L. Christiaen. 2006. Linking chordate gene networks to cellular behavior in ascidians. Cell 124: 247-250.

Davidson, B., W. Shi, and M. Levine. 2005. Uncoupling heart cell specification and migration in the simple chordate Ciona intestinalis. Development 132: 4811-4818.

Davidson, B., and M. Levine. 2003. Evolutionary origins of the vertebrate heart: Specification of the cardiac lineage in Ciona intestinalis. Proceedings of the National Academy of Sciences U.S.A. 100: 11469-11473.

Contact Information

Mailing: Bradley Davidson, Assistant Professor Department of Molecular & Cellular Biology University of Arizona Medical Research Building 313 P.O. Box 245217 Tucson, AZ 85724-0241

Telephone: 520-626-6278 (Office) 520-626-8153 (Lab) Fax: 520-621-3709 Email: bjd18@email.arizona.edu

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