Parker B. Antin
Professor of Cell Biology & Anatomy, and Molecular and Cellular Biology
Ph. D., University of Pennsylvania
Molecular Regulation of Vertebrate Development
E-mail: pba@email.arizona.edu
Research Interests:
Research in our laboratory is focused on understanding the molecular regulation of early developmental processes in vertebrate embryos. We primarily use the chicken embryo as a model organism, and approach research questions from the dual perspective of how individual molecules function and how their functions can be integrated into network models. One present research emphasis is concerned with understanding epithelial to mesenchymal transition (EMT) during avian gastrulation. Studies use gain and loss of function approaches to investigate key transcriptional regulatory proteins and adhesion molecules. One group of molecules of particular emphasis is the Ephs and ephrins, which mediate bidirectional signals between adjacent cells. By modulating cytoskeleton dynamics affecting cell motility and adhesion, Ephs and ephrins orchestrate cell movements during multiple morphogenetic processes including gastrulation, segmentation, angiogenesis, axonal path finding, and neural crest cell migration. We are also exploring the transcriptional regulatory pathway that governs expression of downstream effector molecules such as Ecadherin and the Ephs and ephrins.
These studies are integrating with a parallel effort to generate broad approaches for developing network models of biological processes in vertebrates. This involves high throughput in situ hybridization and microarray gene expression analysis and large scale-collation of published information to generate preliminary network models. Models are then tested through parameter space using software tools such as Ingeneue. Results are integrated with an artificial intelligence software environment that evaluates results and can suggest network modifications for retesting. Promising candidate network models are then tested in vivo. Through successive reiterations between computational network modeling and model testing in vivo, progressively more representative networks can be generated. Initial efforts are focused on modeling EMT during gastrulation, the appearance of endothelial cells from the mesoderm, and organization of endothelial cells into vascular tubes.
Our laboratory also hosts the GEISHA in situ hybridization database and website (http://geisha.arizona.edu). The GEISHA project (gallus expression in situ hybridization analysis) began in 1998 to investigate using high throughput whole mount in situ hybridization to identify novel, differentially expressed genes in chicken embryos. An initial expression screen of approximately 900 genes demonstrated feasibility of the approach, and also highlighted the need for a centralized repository of in situ hybridization expression data. Funding was eventually obtained for this purpose. The goals of the GEISHA project are to obtain whole mount in situ hybridization expression information for all differentially expressed genes in the chicken embryo between HH stages 1-25, to integrate expression data with the chicken genome browsers, and to offer this information through a user-friendly graphical user interface.
Selected Publications:
Zhang, W., Yatskievych, T.A., Xu, C., and Antin, P.B. (2002) Regulation of the homeobox gene Hex by a Smads dependent signaling pathway. J. Biol. Chem. 277: 45435-45441.
Grill, M.G., Bales, M.S., Fought, A.N., Rosburg, K.C., Munger, S.J., and Antin, P.B. (2003) Tetracycline-inducible system for regulation of skeletal muscle-specific gene expression in transgenic mice. Transgenic Res: 12: 33-43.
Kazmierski, S.T., Antin, P.B., Witt, C., Labeit, S., and Gregorio, C.G. (2003) The complete sequence of the mouse nebulin gene and expression of nebulin in the vertebrate heart. J. Mol. Biol.; 328:835-846
Baker, R.K., and Antin, P.B. Ephs and ephrins during early stages of chick embryo development. (2003) Dev. Dyn. : 228:128-142.
Bell, G.W., Yatskievych, T.A., and Antin, P.B. (2004) GEISHA, a high throughput whole mount in situ hybridization screen in chick embryos. Devel. Dynamics 229: 677-687.
Zhang, W., Yatskievych, T.A., Baker, R.B., and Antin, P.B. (2004) Regulation of Hex Gene Expression and Initial Stages of Avian Hepatogenesis by Bmp and Fgf Signaling. Devel. Biol.: 268:309-322.
Vokes, S., Yatskievych, T.A., McMahon, A.P., Heimark, R.L., Antin, P.B., and Krieg, P.A. (2004) Sonic hedgehog signaling is essential for the formation of endothelial tubes during vasculogenesis. Development: 131:4371-4380.
Antin, P.B., and Konieczka, J.H. (2005). Genomic Resources for Chicken. Dev. Dyn.: 232: 877-882.
Ono, Y., Antin, P.B., and Gregorio, C.C. (2005) Disruption in the Tmod1 gene compromises cardiomyocyte development in murine embryonic stem cells by arresting myofibril maturation. Devel Biol. 282: 336-348.
Hardy, K.M., Mjaatvedt, C.H., and Antin, P.B. (2006). Hot hearts in the Sonoran desert: the 11th Weinstein cardiovascular development conference in Tucson. Devel. Dynamics: 235:170-175.
Klewer, S.E, Yatskievych, T.A., Pogreba, K., Antin, P.B., and Camenisch, D. (2006) Has2 expression during cardiogenesis is independent of Bmp signal. Gene Expression Patterns 6:462-470.
Ason, B., Darnell, D.K., Wittbrodt, B., Berezikov, E., Kloosterman, W.P., Wittbrodt, J., Antin, P.B., and Plasterk, R.H.A. (2006). Comparative Analysis of miRNA expression. Proc. Natl. Acad. Sci. USA 103:14385-14389.
Rodgers, L., Lalani, S., Hardy, K.M., Xiang, X., Broka, D., Antin, P.B., and Camenisch, T.D. (2006) Depolymerized Hyaluronan Induces VEGF, a negative regulatory of developmental EMT. Circ. Res. 99:583-589.
Doyle, S.E., Scholz, M.J., Greer, K.A., Darnell, D.K., Antin, P.B., Klewer, S. E., and Runyan, R.B. (2006). Latrophilin-2 is a novel component of the epithelial-mesenchymal transition within the atrioventricular canal of the embryonic chicken heart. In press.
Darnell, D.K. Kaur, S., Stanislaw, S., Konieczka, J.H., Yatskievych, T.A., and Antin, P.B. MicroRNAs during chicken embryo development.(2006) Devel. Dyn.: In press.
Darnell, D.K., Kaur, S., Stanislaw, S., Davey, S., Konieczka, J.H., Yatskievych, T.A., and Antin, P.B. GEISHA: An In situ hybridization gene expression resource for the chicken embryo. Cytogenet. Genome Res.: In press.
