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Molecular Biology

Steven Britt
Associate Professor
M.D. (1986), University of Texas Medical Branch - Galveston


Visual system development and function using molecular-genetic approaches in Drosophila

Color vision is dependent upon the expression of spectrally distinct visual pigments in different classes of photoreceptor cells. This requires both a developmental program that generates different types of photoreceptor cells, and a collection of unique visual pigments having different spectral properties. My lab is working on aspects of both of these problems using the fruit fly, Drosophila melanogaster, as an experimental system.

Photoreceptor cell-fate determination and the regulation of visual pigment gene expression: The compound of eye of Drosophila is highly patterned and has been used extensively as a model system in developmental biology. We have found that the cell fate and visual pigment expression pattern of adjacent photoreceptor cells is tightly coordinated. It appears that one retinal cell type in each ommatidium (R7) adopts one of two different cell fates in a stochastic manner, and then communicates this decision (inductively) to the adjacent R8 cell. These events coordinate the expression of the visual pigments in these two cells, and produce two types of optical units within the eye that have distinct spectral sensitivities.

To examine this process at a genetic and molecular level, we have identified a collection of mutants that have a variety of defects in photoreceptor cell fate determination and visual pigment gene expression. These mutants define genes that are required for the normal patterning of the eye. One group of mutants shows  defects in the stochastic determination event within the R7 cell, and another group appears to have defects in the inductive signal to the R8 cell. We are currently characterizing these mutations and beginning the molecular analysis of the affected genes

Visual pigment studies: We are also examining how the structures of different visual pigments regulate their absorption spectra and photochemical properties. We have identified specific amino acid residues that are responsible for regulating UV vs. visible and blue vs. green absorption, and we are also examining the spectral tuning of metarhodopsin, the activated form of the visual pigment rhodopsin. In collaborative studies, we have examined the mechanism of photoactivation and characterized the photo-intermediates of the Drosophila rhodopsins using low temperature spectroscopic methods. We are also studying the visual pigments of other invertebrate organisms.


Selected Publications

Britt, S.G., Feiler, R., Kirschfeld, K., and Zuker, C.S. (1993) Spectral tuning of rhodopsin and metarhodopsin in vivo. Neuron, 11, 29-39.

Chou, W.-H., Hall, K.J., Wilson, D.B., Wideman, C.L., Townson, S.M., Chadwell, L.V., and Britt, S.G. (1996) Identification of a novel Drosophila opsin reveals specific patterning of the R7 and R8 photoreceptor cells. Neuron, 17, 1101-1115.

Vinos, J., Jalink, K., Hardy, R.W., Britt, S.G., Zuker, C.S. (1997) A G protein-coupled receptor phosphatase required for rhodopsin function.Science, 277, 687-690.

Townson, S.M., Chang, B.S.W., Salcedo, E., Chadwell, L.V., Pierce, N.E., and Britt, S.G. (1998) Honeybee blue- and ultra-violet-sensitive opsins: Cloning, heterologous expression in Drosophila and physiological characterization. J. Neurosci., 18, 2412-2422.

Chou, W.-H., Huber, A., Bentrop, J., Schulz, S., Schwab, K., Chadwell, L.V., Paulsen, R., and Britt, S.G. (1999) Patterning of the R7 and R8 photoreceptor cells of Drosophila: Evidence for induced and default cell-fate specification. Development, 126, 607-616.

Salcedo, E., Huber, A., Henrich, S., Chadwell, L.V., Chou, W.-H., Paulsen, R., and Britt, S.G. (1999) Blue- and green-absorbing visual pigments of Drosophila: Ectopic expression and physiological characterization of the R8 photoreceptor cell-specific Rh5 and Rh6 rhodopsins. J. Neurosci., 19, 10716-10726.

Vought, B.W., Salcedo, E., Chadwell, L.V., Britt, S.G., Birge, R.R., and Knox, B.E. (2000) Characterization of the primary photointermediates of Drosophila rhodopsin . Biochemistry, 39, 14128-14137.

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