Steven G. Britt Associate Professor Cell and Developmental Biology / Ophthalmology M.D., University of Texas Medical Branch - Galveston, 1986 UC D - Anschutz Medical Campus RC1-South, Rm 12100 Mail Stop 8108 12801 East 17th Ave Aurora, CO 80045 Phone: 303-724-3441 Fax: 303-724-3420 Email: Steve.Britt@ucdenver.edu

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Departmental Affiliations Cell and Developmental Biology Ophthalmology

Other Graduate Program Affiliations Biomedical Sciences Program (BSP) Medical Scientist Training Program (MSTP) Neuroscience Molecular Biology

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:

	Dissociated ommatidia demonstrate paring between Rh4 expressing R7 photoreceptor cells (blue) and Rh6 expressing R8 cells (red). The R1-6 photoreceptors express Rh1 (green).

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

Bell ML, Earl JB, Britt SG. Two types of Drosophila R7 photoreceptor cells are arranged randomly: a model for stochastic cell-fate determination. J Comp Neurol. 2007 May 1;502(1):75-85. J Comp Neurol. 2007 May 1;502(1):75-85.

Earl JB, Britt SG. Expression of Drosophila rhodopsins during photoreceptor cell differentiation: insights into R7 and R8 cell subtype commitment. Gene Expr Patterns. 2006 Oct;6(7):687-94. Gene Expr Patterns. 2006 Oct;6(7):687-94. Epub 2006 Feb 21.

Salcedo E, Zheng L, Phistry M, Bagg EE, Britt SG. Molecular basis for ultraviolet vision in invertebrates. J Neurosci. 2003 Nov 26;23(34):10873-8.

Knox BE, Salcedo E, Mathiesz K, Schaefer J, Chou WH, Chadwell LV, Smith WC, Britt SG, Barlow RB. Heterologous expression of limulus rhodopsin. J Biol Chem. 2003 Oct 17;278(42):40493-502. Epub 2003 Jun 23.

Vought BW, Salcedo E, Chadwell LV, Britt SG, Birge RR, Knox BE. Characterization of the primary photointermediates of Drosophila rhodopsin. Biochemistry. 2000 Nov 21;39(46):14128-37.

Salcedo E, Huber A, Henrich S, Chadwell LV, Chou WH, Paulsen R, Britt SG. 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. 1999 Dec 15;19(24):10716-26.

Chou WH, Huber A, Bentrop J, Schulz S, Schwab K, Chadwell LV, Paulsen R, Britt SG. Patterning of the R7 and R8 photoreceptor cells of Drosophila: evidence for induced and default cell-fate specification. Development. 1999 Feb;126(4):607-16.

Latest Publications in PubMed