- Murine Pkd1 is a
developmentally regulated gene from morula to adulthood:
role in tissue condensation and patterning. Guillaume
R, D'Agati V, Daoust M, Trudel M Dev Dyn 1999
Apr;214(4):337-48
- 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. PMID: 10213389, UI:
99228403
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