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Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development
Véronique Chauvet1, Feng Qian, Nicolas Boute
1INSERM U423 and the Département deGénétique et Unité INSERM U393, Hôpital Necker-Enfants Malades, Paris, France.
Insights
Autosomal-dominant polycystic kidney disease genes PKD1 and PKD2 show distinct expression patterns during human kidney development. PKD2 is widely expressed early, while PKD1 appears later in proximal tubules, suggesting different roles in nephrogenesis.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder caused by mutations in PKD1 or PKD2.
- Polycystin-1 (P1) and Polycystin-2 (P2) are transmembrane proteins encoded by these genes.
- The precise tissue distribution and developmental roles of P1 and P2, particularly P1, remain incompletely understood.
Purpose of the Study:
- To investigate the spatiotemporal expression patterns of PKD1 and PKD2 transcripts and proteins during human embryogenesis and kidney development.
- To clarify the differing roles of polycystins in nephrogenesis.
Main Methods:
- Northern blot analysis to examine transcript expression.
- In situ hybridization for precise localization of gene expression.
- Immunohistochemical methods to detect protein distribution.
Main Results:
- PKD1 and PKD2 transcript and protein expression patterns were concordant.
- Both genes were widely expressed in early human embryos (5-6 weeks) in neural tissue, heart, endoderm, and mesonephros.
- PKD2 was detected in the ureteric bud and metanephros early on, while PKD1 was not.
- PKD2 showed diffuse expression throughout nephron development, whereas PKD1 expression emerged later in proximal tubules.
- PKD1 expression decreased in later fetal stages and was absent in adult kidneys, while PKD2 expression persisted.
Conclusions:
- Significant differences exist in the spatiotemporal expression of PKD1 and PKD2 during human kidney development.
- PKD2 expression is earlier and more widespread than PKD1 during nephrogenesis.
- These distinct expression profiles suggest that polycystins may interact with different partners during kidney development, potentially influencing distinct cellular functions.
Abstract:
Autosomal-dominant polycystic kidney disease, one of the most frequent human genetic disorders, is genetically heterogeneous. Most cases result from mutations of PKD1 or PKD2 encoding polycystin-1 or polycystin-2, respectively. Polycystin-1 is a large transmembrane protein containing several domains involved in cell-cell and/or cell-matrix interactions. Polycystin-2 is transmembrane glycoprotein sharing homology with some families of cation channels. Despite a large number of reports, the tissue distribution of these two proteins, especially of polycystin-1, is still debated. We investigated the expression pattern of PKD1 and PKD2 transcripts and proteins during human embryogenesis and kidney development, using Northern blot analysis, in situ hybridization, and immunohistochemical methods. For each gene, the expression pattern of transcripts and protein was concordant. In human 5- to 6-week-old embryos, both genes are widely expressed, mainly in neural tissue, cardiomyocytes, endodermal derivatives, and mesonephros. At this age, PKD2 but not PKD1 expression is observed in the ureteric bud and the uninduced metanephros. Thereafter, PKD2 is diffusely expressed at all stages of nephron development, whereas high PKD1 expression first appears in differentiated proximal tubules. Proximal tubule expression of both genes decreases from weeks 20 to 24 onwards. PKD1 transcripts, later restricted to distal tubules in fetal nephrogenesis, are no longer detected in adult kidneys, which nevertheless maintain a faint expression of polycystin-1, whereas persistent expression of PKD2 transcripts and protein is observed throughout nephrogenesis. Overall, contrary to previous observations, we found profound differences in the spatiotemporal expression of PKD1 and PKD2 during nephrogenesis, PKD2 being expressed earlier and more diffusely than PKD1. These data suggest that polycystins could interact with different partners, at least during kidney development.