Identification and Expression Analysis of the Complete Family of Zebrafish pkd Genes

Abstract

Polycystic kidney disease (PKD) proteins are trans-membrane proteins that have crucial roles in many aspects of vertebrate development and physiology, including the development of many organs as well as left-right patterning and taste. They can be divided into structurally-distinct PKD1-like and PKD2-like proteins and usually one PKD1-like protein forms a heteromeric polycystin complex with a PKD2-like protein. For example, PKD1 forms a complex with PKD2 and mutations in either of these proteins cause Autosomal Dominant Polycystic Kidney Disease (ADPKD), which is the most frequent potentially-lethal single-gene disorder in humans. Here, we identify the complete family of <i>pkd</i> genes in zebrafish and other teleosts. We describe the genomic locations and sequences of all seven genes: <i>pkd1, pkd1b, pkd1l1, pkd1l2a, pkd1l2b, pkd2</i>, and <i>pkd2l1</i>. <i>pkd1l2a/pkd1l2b</i> are likely to be ohnologs of <i>pkd1l2</i>, preserved from the whole genome duplication that occurred at the base of the teleosts. However, in contrast to mammals and cartilaginous and holostei fish, teleosts lack <i>pkd2l2</i>, and <i>pkdrej</i> genes, suggesting that these have been lost in the teleost lineage. In addition, teleost, and holostei fish have only a partial <i>pkd1l3</i> sequence, suggesting that this gene may be in the process of being lost in the ray-finned fish lineage. We also provide the first comprehensive description of the expression of zebrafish <i>pkd</i> genes during development. In most structures we detect expression of one <i>pkd1</i>-like gene and one <i>pkd2</i>-like gene, consistent with these genes encoding a heteromeric protein complex. For example, we found that <i>pkd2</i> and <i>pkd1l1</i> are expressed in Kupffer's vesicle and <i>pkd1</i> and <i>pkd2</i> are expressed in the developing pronephros. In the spinal cord, we show that <i>pkd1l2a</i> and <i>pkd2l1</i> are co-expressed in KA cells. We also identify potential co-expression of <i>pkd1b</i> and <i>pkd2</i> in the floor-plate. Interestingly, and in contrast to mouse, we observe expression of all seven <i>pkd</i> genes in regions that may correspond to taste receptors. Taken together, these results provide a crucial catalog of <i>pkd</i> genes in an important model system for elucidating cell and developmental processes and modeling human diseases and the most comprehensive analysis of embryonic <i>pkd</i> gene expression in any vertebrate.