COBRE: AMR: WNT SIGNALING & RETINAL REGULATION OF CIRCADIAN RHYTHMICITY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The absence of the Wnt signaling in the canonical pathway is shown to de-repress a cascade of target genes, some of which are implicated to be able to induce or suppress the formation of the forebrain, the midbrain and hindbrain boundary (MHB), the hindbrain, and eyes. Both the brain and eyes (particularly the retinas) are believed to be autonomous circadian oscillators and many key circadian clock genes are rhythmically expressed in the brain and eyes in a robust fashion in zebrafish (Danio rerio). Yet, little is known about how the Wnt signaling regulates circadian rhythmicity and the presumable Wnt signaling target genes that may control daily oscillations of the circadian clock genes. masterblind (mbl) is an ethyl nitrosourea (ENU)-induced mutant generated in a large-scale zebrafish mutagenesis. Zebrafish embryos homozygous for the masterblind (mbl) mutation exhibit reduced or absent eyes and telencephalon, and the expansion of the diencephalic fates to the front of the brain. A mutation in the GSK3-binding domain of zebrafish axin1, a scaffolding protein in the Wnt signaling pathway, results in the eyeless mbl phenotype. It appears that the repression of axin1 and therefore unknown Wnt target genes during the normal development secures the eye formation. In this proposed study, we plan to determine whether mbl disrupts the normal oscillations of circadian clock genes in the retinas and to identify the presumable Wnt target genes that may controls the circadian regulation using microarrays.