Meeting Abstract

15.3  Monday, Jan. 4  Molecular and functional characterization of the zebrafish clusterin gene: Specific expression in the developing choroids plexus and regulation by Notch signaling JIAO, Shuang*; LU, Ling; JIANFENG , Zhou; YUN, Li; CUNMING , Duan; University of Michigan; Ocean University of China; Ocean University of China; Ocean University of China; University of Michigan cduan@umich.edu

Clusterin, also known as Apolipoprotein J, is a secreted glycoprotein associated with many pathological states, including cancer, atherosclerosis, diabetes, renal and neurodegenerative diseases. Clusterin has been proposed to act as an extracellular chaperone that inhibits protein aggregation and precipitation caused by physical or chemical stresses. It is poorly understood when, where, and how its gene expression is regulated in vivo. We have cloned and characterized the zebrafish clusterin gene and studied its gene expression and regulation. The structure of zebrafish clusterin gene and protein is similar to its human homologue. There is a strong syntheny relationship between the fish and human homologues. Biochemical assays show that zebrafish clusterin is a secreted protein. In adult zebrafish, clusterin mRNA is detected in multiple tissues. During early development, clusterin mRNA became dateable at 12 hpf and its levels gradually increased as embryos grow. In situ hybridization analysis indicates that clusterin mRNA is highly expressed in the diencephalic and myelencephalic choroid plexus (ChP) in advanced embryos. Among various stresses tested, heat shock, but not hypoxia or osmotic stresses, increases the levels of clusterin mRNA. Specific inhibition the IGF-1 receptor-mediated signaling and overexpression of IGF ligands did not change clusterin mRAN levels in zebrafish embryos. Inhibition of Notch signaling caused a significant increased in the number of clusterin mRNA-expression cells and in clusterin mRNA levels. These results suggest that clusterin is a marker of ChP and its expression is under the regulation of Notch but not IGF signaling