Education

• B.S., Biology, Southwest Missouri State University, 1984
• M.S., Biology, Southwest Missouri State University, 1986
• Ph.D., Biochemistry & Molecular Biology, University of Kansas Medical Center, 1991
• Postdoctoral Research, Anatomy & Cell Biology, University of Kansas Medical Center, 1991

Contact Information

Research Interests

My laboratory studies the regulation of genes in retinal photoreceptors, with a focus on the genes involved in the many changes that occur in the retina in response to the time of day. This ability to temporally regulate physiology is not simply a response to light and dark, but is controlled by a circadian clock, an intrinsic component of vertebrate retinas. Although the molecular mechanism of circadian timing is not known, a common theme to clock function seems to be regulation at the level of gene expression. I have chosen to focus my research on the clock located in retinal photoreceptors in the African clawed frog, Xenopus laevis. These animals are particularly well suited to cellular and molecular analyses of retinal function. We have techniques for culturing Xenopus retinas such that the circadian clock remains functional and entrainable for many days in vitro.

As part of a screen for rhythmic gene products, we recently identified a novel gene that is expressed specifically in Xenopus photoreceptors. This gene is transcriptionally active for only a few hours in the early night, producing peak mRNA levels at around 4 hours after dusk. This rhythmic expression occurs independently of the presence of light/dark cycles which indicates that it is transcriptionally regulated by an intrinsic circadian clock. This gene encodes a protein that we have named "nocturnin." The protein sequence is novel, but it contains a leucine zipper-like motif and a large region of similarity to a yeast transcription factor called CCR4. Based on this sequence analysis, our current hypothesis is that nocturnin may be dimerizing with another protein through its leucine zipper and functioning as a photoreceptor-specific transcription factor. We are currently studying both the function of the nocturnin protein within the retina and the mechanism by which the circadian clock regulates the expression of this gene to produce such striking rhythmicity.

We are also studying the development of the photoreceptor clock in embryonic Xenopus and are currently working to generate transgenic Xenopus embryos to study the function and expression of nocturnin and other rhythmic gene products. Generation of transgenic lines expressing rhythmic reporters will further extend our studies by allowing real time analysis of gene expression in living embryos.

Representative Publications

1. Green, C.B. and Besharse, J.C. Tryptophan hydroxylase expression is regulated by a circadian clock in Xenopus laevis retina. 1994. J. Neurochem.,62: 2420-2428.
2. Green, C.B., Cahill, G.M., and Besharse, J.C. Regulation of tryptophan hydroxylase expression by a retinal circadian oscillator in vitro. 1995. Brain Res., 677: 283-290.
3. Green, C.B., Cahill, G.M., and Besharse, J.C. Tryptophan hydroxylase is expressed by photoreceptors in Xenopus laevis retina. 1995. Vis. Neurosci., 12(4): 663-670.
4. Green, C.B. and Besharse, J.C. Use of a high stringency differential display screen for identification of retinal mRNAs that are regulated by a circadian clock. 1996. Mol. Brain Res., 37: 157-165.
5. Green, C.B. and Besharse, J.C. Identification of a novel vertebrate circadian clock regulated gene encoding the protein nocturnin. 1996. Proc. Natl. Acad. Sci. USA, 93: 14884-14888.
6. Green, C.B. and Besharse, J.C. Identification of Vertebrate Circadian Clock-Regulated Genes by Differential Display. 1997. In: Methods in Molecular Biology, Differential Display Methods and Protocols, P. Liang and A.B. Pardee, eds. Humana Press Inc., Totowa, New Jersey.
7. Zhu, H. and Green, C.B. (2001) Three cryptochromes are rhythmically
   expressed in Xenopus laevis retinal photoreceptors. Mol. Vis. 7:
   210-5.
8. Zhu, H. and Green, C.B. (2001) Both Xenopus CRY1 and CRY2 functions
   require an intact flavin-binding domain, but are differentially
   sensitive to mutations in a putative flavin electron transport
   pathway. Current Biol., 11: 1945-1949.
9. Hayasaka, N., LaRue, S., and Green, C.B. (2002) In vivo disruption
   of Xenopus CLOCK in the retinal photoreceptor cells abolishes
   circadian melatonin rhythmicity without affecting its production
   levels. J. Neuroscience, 22: 1600-1607.
10. Liu, X. and Green, C.B. (2002) Circadian regulation of nocturnin
    transcription by phosphorylated CREB in Xenopus retinal photoreceptor
    cells. Mol. Cell Biol. 22: 7501-7511.
11. Green, C.B. Molecular control of Xenopus retinal circadian rhythms.
    J. Neuroendocrinol., in press.
12. Baggs, J. and Green, C.B. Nocturnin, a rhythmically expressed
    deadenylase in Xenopus laevis retina: a mechanism for
    post-transcriptional control of circadian-related mRNA. Current
    Biol., in press.