Xenopus tropicalis as a model organism for genetics and genomics: past, present, and future

Abstract

Xenopus tropicalis was introduced as a model system for genetic, and then genomic research, in the early 1990s, complementing work on the widely used model organism Xenopus laevis. Its shorter generation time and diploid genome has facilitated a number of experimental approaches. It has permitted multigenerational experiments (e.g., preparation of transgenic lines and generation of mutant lines) that have added powerful approaches for research by the Xenopus community. As a diploid animal, its simpler genome was sequenced before X. laevis, and has provided a highly valuable resource indispensable for all Xenopus researchers. As more sophisticated transgenic technologies for manipulating gene expression are developed, and mutations, particularly null mutations, are identified in widely studied genes involved in critical cellular and developmental processes, researchers will increasingly turn to X. tropicalis for definitive analysis of complex genetic pathways. This chapter describes the historical and conceptual development of X. tropicalis as a genetic and genomic model system for higher vertebrate development.

Figure 1

Images of X. tropicalis developmental mutants. Two X. tropicalis mutants identified during a gynogenetic screen of wild caught animals are shown in A-F. A and B, images of wild type and mutant little pitcher embryos, respectively. Otoconia are missing in the mutant inner ear (demarcated by the black arrow in wildtype embryos) and the inner ear vesicle is enlarged (indicated by dotted circle). C and D, images of wild type and mutant cataract embryos, respectively. The lens area appears very cloudy in the mutant embryos (white arrow). Sections of wild type and mutant embryos in E and F, respectively, reveal a highly reduced lens size in cataract embryos (black arrows). G. Metamorphosing xenopus de milo (xdm) froglets (two mutant; one wildtype). The striking absence of forelimbs illustrates the kind of mutation that is likely to be particularly insightful for clarifying tetrapod development. This mutation was found to interrupt the nephronectin gene, which produces a small integrin ligand, now clearly implicated in forelimb development. Image courtesy of L. Zimmerman (National Institute for Medical Research, Mill Hill, London).

Figure 2

Participants in a Bay Area Regional Frog meeting in late 1992 in which the prospects for the X. tropicalis system were discussed. Participants included, from left to right, Marc Kirschner, Jeremy Green, Pascal Stein, Andre Brandli, Tabitha Doniach, William Smith, Kristen Kroll, Michael Sheets, Richard Harland, Enrique Amaya, John Gerhart, Robert Davis and Lyle Zimmerman.