In the past several years the PI's laboratory has extensively characterized the tissue interactions responsible for induction of the embryonic lens, and this has led him to define four major stages in the lens determination process: competence, bias, specification and differentiation. Each of these stages can now be monitored by biological assays he has developed. At the same time, he, and others, have characterized a number of genes encoding transcription factors that either have been shown to be involved in eye determination or are likely candidates for such a function. New technological breakthroughs, e.g., a useful procedure for transgenesis in Xenopus, now permit a number of strategies for evaluating gene function. Utilizing this information about the biology and molecular genetics of lens determination, and new technical advances, he proposes a series of experiments to test the function of putative regulatory genes in lens determination in mouse and Xenopus embryos. The first goal is to examine promoter regulation of Xenopus crystallin genes. The second goal is to clone and characterize expression of members of two newly discovered gene families likely to be important in lens determination. The third goal is to define further the genetic hierarchy controlling eye determination by using mouse mutants and genetic interference experiments in Xenopus to assess genetic interactions. The final goal is to test the function of transcriptional regulatory genes in controlling lens competence, bias and specification in Xenopus embryos.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010283-08
Application #
6329541
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1993-12-01
Project End
2004-11-30
Budget Start
2000-12-01
Budget End
2004-11-30
Support Year
8
Fiscal Year
2001
Total Cost
$232,152
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Plautz, Carol Zygar; Zirkle, Brett E; Deshotel, Malia J et al. (2014) Early stages of induction of anterior head ectodermal properties in Xenopus embryos are mediated by transcriptional cofactor ldb1. Dev Dyn 243:1606-18
Ogino, Hajime; Fisher, Marilyn; Grainger, Robert M (2008) Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification. Development 135:249-58
Ogino, Hajime; McConnell, William B; Grainger, Robert M (2006) Highly efficient transgenesis in Xenopus tropicalis using I-SceI meganuclease. Mech Dev 123:103-13
Ogino, Hajime; McConnell, William B; Grainger, Robert M (2006) High-throughput transgenesis in Xenopus using I-SceI meganuclease. Nat Protoc 1:1703-10
Sullivan, Charles H; Braunstein, Leslie; Hazard-Leonards, Royce M et al. (2004) A re-examination of lens induction in chicken embryos: in vitro studies of early tissue interactions. Int J Dev Biol 48:771-82
Hirsch, Nicolas; Zimmerman, Lyle B; Gray, Jessica et al. (2002) Xenopus tropicalis transgenic lines and their use in the study of embryonic induction. Dev Dyn 225:522-35
Chae, Jeiwook; Zimmerman, Lyle B; Grainger, Robert M (2002) Inducible control of tissue-specific transgene expression in Xenopus tropicalis transgenic lines. Mech Dev 117:235-41
Hirsch, Nicolas; Zimmerman, Lyle B; Grainger, Robert M (2002) Xenopus, the next generation: X. tropicalis genetics and genomics. Dev Dyn 225:422-33
Curran, K L; Grainger, R M (2000) Expression of activated MAP kinase in Xenopus laevis embryos: evaluating the roles of FGF and other signaling pathways in early induction and patterning. Dev Biol 228:41-56
Enwright 3rd, J F; Grainger, R M (2000) Altered retinoid signaling in the heads of small eye mouse embryos. Dev Biol 221:22-Oct

Showing the most recent 10 out of 13 publications