My laboratory studies the evolution of developmental mechanisms using molecular, cellular, and genetic approaches. We use two animal systems in this research: teleost fishes and ascidians. The teleost Astyanax fasciatus is used to study the evolution of eye development. Astyanax populations living in surface streams have large eyes and pigmentation, whereas those adapted to limestone caves have lost their eyes and pigmentation. Astyanax is one of the few cases in which the ancestral and derived developmental states are available for comparative analysis in the same species. Eye development is initiated in the cave fish embryo but the eye arrests later in development. We are studying the molecular basis of eye degeneration. Cave fish embryonic lens cells undergo extensive programmed cell death, which has widespread effects on eye development. Transplantation experiments indicate that a lens obtained from a surface fish donor is sufficient to rescue eye development in a cave fish host, showing that the lens is a major regulator of eye degeneration. Current studies include the molecular regulation of lens apoptosis and the antagonism between the pax6, pax2, and midline signaling genes, which appears to be responsible for the regression of eye development in cave fish. We are also studying the evolution of eye regression in different cave fish populations, which appear to have evolved independently. In these studies, we seek to understand whether parallel evolution has occurred by the same or different mechanisms.

The developmental mechanisms we are studying in ascidians, one of the most simple chordates, may shed light on the origin of more complex developmental patterns in vertebrates. Most ascidian species develop via a tadpole larva, which contains a tail with a notochord and other typical chordate features. However, a few ascidian species develop via a tailless larva. Phylogenetic studies suggest that the tailless species evolved several different times from tailed ancestors. Most of our studies are done with the sister species Molgula oculata, a tailed species, and Molgula occulta, a tailless species. These species can be hybridized. When sperm of the tailed species are used to fertilize eggs of the tailless species, the development of the tail and other chordate features is restored, while the reciprocal fertilization has no effect on the tailed larva. We are studying the genetic pathway required for restoration of the tail and other chordate features and how it has been changed in the tailless species. The zinc finger gene Manx and the closely-linked bobcat gene, which encodes an DEAD-box RNA helicase, are required for tail restoration. The forkhead gene FH1, a relative of the vertebrate HNF-3? gene, is also involved in tail formation and restoration. Problems currently being investigated are the interrelationships and cellular functions of these "tail-forming" genes.

 

Examples of Recent Publications:

Jeffery, W.R., A.G. Strickler, S. Guiney, D. Heyser, and S. I. Tomarev (2000) Prox 1 in eye degeneration and sensory compensation during development and evolution of the cavefish Astyanax. Dev. Genes. Evol. 210: 223-230.

Yamamoto, Y, and W. R. Jeffery. (2000) Central role for the lens in cave fish eye degeneration. Science 289: 631-633.

Jeffery, W. R. (2001) Determinants of cell and positional fate in ascidian embryos. Int. Rev. Cytol. 203: 3-62.

Jeffery, W. R. (2001). Cavefish as a model system in evolutionary developmental biology. Develop. Biol. 231: 1-12.

Strickler, A. G., Y. Yamamoto, and W. R. Jeffery. (2001). Early and late changes in Pax 6 expression accompany eye degeneration during cavefish development. Dev. Genes Evol. 211: 138-144.

Jeffery, W. R. (2002). Role of PCNA and ependymal cells in ascidian neural development. Gene 287: 97-105.

Vihtelic, T. S., Y. Yamamoto, M. T. Sweeney, W. R. Jeffery, and D. Hyde (2002). Zebrafish lens mutants display arrest of lens differentiation and epithelial cell degeneration. Develop. Dynam. 222: 625-636.

Dowling, T. E., D. P., Martasian, and W. R. Jeffery. (2002). Evidence for multiple genetic lineages with similar eyeless phenotypes in the blind cavefish, Astyanax mexicanus. Mol. Biol. Evol. 19: 446-455.

Strickler, A. G., K. Famuditimi, and W. R. Jeffery. (2002). Role of retinal homeobox genes in cavefish eye degeneration. Int. J. Dev. Biol. 46: 285-294.

Jeffery, W. R. (2002). Programmed cell death in the ascidian embryos: Modulation by Fox5A5 and Manx and roles in the evolution of larval development. Mech. Develop. 118: 11-124.

Jeffery, W. R. (2002). Ascidian gene expression profiles. Genome Biol. 3: 1030.1-1030.4

Yamamoto, Y., and W. R. Jeffery. (2002). Probing vertebrate eye development by lens transplantation. Methods 28: 420-426.
 
 

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