Molecular characterization, phylogenetic relationships, and developmental expression patterns of prion genes in zebrafish (Danio rerio)

Abstract

Prion diseases are characterized by the accumulation of a pathogenic misfolded form of a prion protein (PrP) encoded by the Prnp gene in humans. In the present study in zebrafish, two transcripts and the corresponding genes encoding prion proteins, PrP1 and PrP2, related to human PrP have been characterized with a relatively divergent deduced amino acid sequence, but a well preserved overall organization of structural prion protein motifs. Whole‐mount in situ hybridization analysis performed during embryonic and larval development showed a high level of PrP1 mRNA spatially restricted to the anterior floor‐plate of the central nervous system and in ganglia. Transcripts of prp2 were detected in embryonic cells from the mid‐blastula transition to the end of the segmentation period. From 24 h postfertilization up to larval stages, prp2 transcripts were localized in distinct anatomical structures, including a major expression in the brain, eye, kidney, lateral line neuromasts, liver, heart, pectoral fins and posterior intestine. The observed differential developmental expression patterns of the two long PrP forms, prp1 and prp2, and the short PrP form prp3, a more divergent prion‐related gene previously identified in zebrafish, should contribute to understanding of the phylogenetic and functional relationships of duplicated prion gene forms in the fish genome. Together, the complex history of prion‐related genes, reflected in the deduced structural features, conserved amino acid sequence and repeat motifs of the corresponding proteins, and the presence of differential developmental expression patterns suggest possible acquisition or loss of prion protein functions during vertebrate evolution.

The role of prion protein in stem cell regulation

“…Prnp is phylogenetically conserved in zebrafish since human-related prion protein genes PrP-1 and PrP-2, as well as their transcripts, have been described and a less human-related isoform PrP3 has been recently found (Cotto et al 2005). RNA deep sequencing of transcriptomes in early development showed that only PrP-2 persisted as maternal RNA until early gastrula (5.3 hpf), the other isoforms were not detected at this stage.…”

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

“…The fabp2 probe was 203 bp long. The protocol for in situ hybridization was as previously described ( 51,52 ), except that prehybridization and hybridization were conducted at 60°C. The posthybridization stringent baths were at hybridization temperature, except for the last two baths in 0.2× SSC Tween at 57°C (30 min each).…”

Functional Implication of Cellular Prion Protein in Antigen-Driven Interactions between T Cells and Dendritic Cells

“…Besides a complete resistance to TSE infectious propagation (7), mice lacking PrPC (PrP Ϫ ) display only minor phenotypic anomalies (8,9). Yet, the remarkable conservation of Prnp, the PrPCencoding gene (Ͼ85% homology between mouse and human sequences) and its universal expression in vertebrate species (10,11), suggests that the gene product fulfills either directly or indirectly, some vital function(s). Deciphering the biological role of PrPC is therefore a major challenge for an evolutionary interpretation of the Prnp gene conservation and for a better understanding of TSE pathogenesis.…”