Transcriptomic analysis of zebrafish prion protein mutants supports conserved cross-species function of the cellular prion protein

Cellular Prion Protein (PrP^C) is a well-studied protein as the substrate for various progressive untreatable neurodegenerative diseases. Normal functions of PrP^C are poorly understood, though recent proteomic and transcriptomic approaches have begun to reveal common themes. We use our compound <i>prp1</i> and <i>prp2</i> knockout mutant zebrafish at three days post fertilization to take a transcriptomic approach to investigating potentially conserved PrP^C functions during development. Gene ontology analysis shows the biological processes with the largest changes in gene expression include redox processing, transport and cell adhesion. Within these categories several different gene families were prevalent including the solute carrier proteins, cytochrome p450 enzymes and protocadherins. Continuing from previous studies identifying cell adhesion as an important function of PrP^C we found that in addition to the protocadherins there was a significant reduction in transcript abundance of both <i>ncam1a</i> and <i>st8sia2</i>. These two genes are involved in the early development of vertebrates. The alterations in cell adhesion transcripts were consistent with past findings in zebrafish and mouse prion protein mutants; however E-cadherin processing after prion protein knockdown failed to reveal any differences compared with wild type in either our double <i>prp1/prp2</i> mutant fish or after <i>prp1</i> morpholino knockdown. Our data supports a cross species conserved role for PrP^C in the development and maintenance of the central nervous system, particularly by regulating various and important cell adhesion processes.