The International Journal of Developmental Biology

Int. J. Dev. Biol. 62: 637 - 640 (2018)

Pkd2 deletion during embryo development does not alter mesonephric programmed cell senescence

Sabela Da Silva-Álvarez1, Olaya Lamas-González2, Alba Ferreirós1, Patricia González3, María Gómez3, Tomás García-Caballero3, Miguel González Barcia4, Miguel A. García-González*,2 and Manuel Collado*,1

>1Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), XXIS/SERGAS, 2Laboratorio de Genética y Biología del Desarrollo de las Enfermedades Renales, Instituto de Investigación Sanitaria (IDIS), XXIS/SERGAS, 3Histopathology Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid, 4Departamento de Ciencias Morfológicas, Facultad de Medicina. USC. XXIS/SERGAS, 5Servicio de Farmacia, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain


Programmed cell senescence during embryo development is a recently described process that opens a new perspective to understand the senescence response and that adds a new player whose contribution to development needs to be addressed. Identifying developmental syndromes with a root in deregulated programmed cell senescence will undoubtedly reinforce our view of senescence and could provide a new angle to confront disease. One of the structures that was initially reported to undergo cellular senescence is the mesonephros. During E12.5-E14.5, before regression, mesonephric tubules are positive for the most widely used marker of cell senescence, SAβG, and negative for proliferation marker, Ki67, in a p21Cip1-dependent manner. PKD2 is one of the genes defective in autosomal dominant polycystic kidney disease (ADPKD). Inherited mutations in this gene result in cyst formation in adults after a secondary hit. Polycystin-2 (PC2) protein, the product of PKD2 gene expression, inhibits cell cycle progression by inducing p21Cip1, whereas mutated PKD2 results in increased proliferation and defective differentiation of kidney epithelial cells. Here, we addressed the possibility of defective programmed cell senescence as a consequence of Pkd2 deletion in mice. We analyzed embryos for the expression of the senescence marker SAβG, for the proliferative status of mesonephric tubule cells, and for the expression of p21Cip1, without identifying any noticeable deregulation of cell senescence. Our results exclude defective programmed cell senescence upon Pkd2 ablation as an initial event in ADPKD.


Pkd2, cellular senescence, development, mesonephros

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