Spatio-Temporal Expression Pattern of CAKUT Candidate Genes DLG1 and KIF12 during Human Kidney Development

We aimed to investigate expression of the novel susceptibility genes for CAKUT, DLG1 and KIF12, proposed by a systematic in silico approach, in developing and postnatal healthy human kidneys to provide information about their spatiotemporal expression pattern. We analyzed expression of their protein products by immunohistochemistry and immunofluorescence and quantified relative mRNA levels by RT-qPCR. Statistically significant differences in expression patterns were observed between certain developmental stages. Strong expression of DLG1 was observed in the developing kidney, with a gradual decrease from the first phase of kidney development (Ph1) until the third phase (Ph3), when most nephrons are formed; at later stages, the highest expression was observed in the tubules. KIF12 was highly expressed in the developing structures, especially in Ph1, with a gradual decrease until the postnatal phase, which would indicate a significant role in nephrogenesis. Co-localization of DLG1 and KIF12 was pronounced in Ph1, especially on the apical side of the tubular epithelial cells. Thereafter, their expression gradually became weaker and was only visible as punctate staining in Ph4. The direct association of DLG1 with KIF12 as control genes of normal kidney development may reveal their new functional aspect in renal tubular epithelial cells.

Automated summary

We investigated the expression of two novel susceptibility genes, DLG1 and KIF12, in healthy human kidneys during development and postnatal stages. DLG1 showed strong expression in the developing kidney, gradually decreasing until the third phase and exhibiting highest expression in the tubules at later stages. KIF12 was highly expressed during development, especially in the first phase, and gradually decreased until the postnatal phase, suggesting its significant role in nephrogenesis. Co-localization of DLG1 and KIF12 was observed in the early phase, particularly in the tubular epithelial cells, indicating a potential functional aspect in renal development.