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Molecular genetics of eye development and vision
Color vision is dependent upon the presence of photoreceptor neurons that are sensitive to different colors of light. This requires both a developmental program that generates different types of photoreceptor cells, and a collection of light sensitive pigments, expressed in different cells, that detect different colors of light. My lab is working on the molecular genetics of both of these problems using the fruit fly, Drosophila melanogaster. 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 the eye adopts one of two different cell fates in a stochastic (random) manner, and then communicates this decision (inductively) to the adjacent photoreceptor 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 color 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 eye development. 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, and another group has defects in the inductive signal between adjacent cells. 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 color sensitivity. We have identified specific amino acid residues that are responsible for regulating UV vs. visible and blue vs. green sensitivity. Interestingly, these same amino acid sites in human and other vertebrate visual pigments are also responsible for tuning color sensitivity. Mutations at these sites may also lead to inherited forms of blindness. In addition, these same amino acid sites in human neurotransmitter receptors regulate the binding of transmitters and drugs as well as receptor activation. Selected Publications
Birkholz DA, Chou WH, Phistry MM, Britt SG. rhomboid mediates specification of blue- and green-sensitive R8 photoreceptor cells in Drosophila. J Neurosci. 2009 Mar 4;29(9):2666-75. Salcedo E, Farrell DM, Zheng L, Phistry M, Bagg EE, Britt SG. The green-absorbing Drosophila Rh6 visual pigment contains a blue-shifting amino acid substitution that is conserved in vertebrates. J Biol Chem. 2009 Feb 27;284(9):5717-22. 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. |
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