Murine Pkd1 is a developmentally regulated gene from morula to adulthood: role in tissue condensation and patterning.
PKD1 is the most common genetically mutated gene involved in autosomal dominant polycystic kidney disease (ADPKD). Our previous studies have shown that the pathogenesis of human and murine polycystic kidney disease (PKD) involves failure to switch out of a renal developmental program, suggesting a role for PKD1 in development. To investigate this hypothesis, we have cloned a portion of the murine Pkd1 gene and characterized the fetal to adult tissue expression pattern of Pkd1. We chose to clone the transmembrane region of Pkd1, a region prone to mutations in ADPKD. The transmembrane coding region (2.6 kb) has 80.3% nucleotide homology with human PKD1 and 85.3% amino acid similarity. The cloned murine Pkd1 fragment closely resembles that of human PKD1 with respect to both genomic size and exon/intron position. We have demonstrated that this Pkd1 region is not conserved in lower organisms and is mammalian specific. A detailed expression analysis of Pkd1 revealed expression as early as the morula stage and in ES cells with differential expression levels in various tissues/organs throughout development. Highest expression levels were observed in the early condensing mesenchyme of primitive mesoderm and ectoderm. Pkd1 was also expressed at high levels in developing neural tube, neural crest derivatives, prechondrogenic tissue, metanephros, bladder, salivary glands, lung, and blood vessels with lower expression levels in other organs and tissues. Specific spatial and temporal patterns of Pkd1 expression were demonstrated in individual organs, such as lung, kidney, brain, indicating it is highly developmentally regulated. Particularly high levels persisted in mature derivatives of neural tube, neural crest, chondrogenic tissue, metanephros, and lung. In summary, our data suggest that Pkd1 has at least two cellular functions, one a basic function involved in early tissue condensation processes, and the other a mammalian-specific function, that evolved with tissue patterning and tubulogenesis in metanephric and pulmonary development.
Guillaume
R
R
Institut de Recherches Cliniques de Montréal, Molecular Genetics and Development, Faculté de Médecine de l'Université de Montréal, Quebec, Canada.
D'Agati
V
V
Daoust
M
M
Trudel
M
M
D000818:Animals; D015139:Blotting, Southern; D019521:Body Patterning; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008957:Models, Genetic; D009432:Neural Crest / Q000196:embryology; D009865:Oocytes / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism; D050396:TRPP Cation Channels; D013997:Time Factors; D014018:Tissue Distribution
D018076:DNA, Complementary; D011506:Proteins; D050396:TRPP Cation Channels