BioProject

A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. More...

A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germline is unknown. Here we uncover that TAp73 unexpectedly functions as adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73KO and p73KO mice, but not ΔNp73KO mice, display a ‘near-empty seminiferous tubule’ phenotype due to massive premature loss of immature germ cells. Its cellular basis are defective cell-cell adhesions of developing germ cells to Sertoli nurse cells, with secondary degeneration of Sertoli cells including the blood-testis-barrier, thereby disrupting the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, produced in germ cells, controls a coordinated transcriptional program of adhesion- and migration-related proteins including peptidase inhibitors, proteases, receptors and integrins required for germ-Sertoli cell adhesion and dynamic junctional restructuring. Thus, the testis emerges as unique organ with strict division of labor among all family members: p63 and p53 safeguard germline fidelity, while TAp73 ensures fertility by enabling sperm maturation. Overall design: 3 mice each for control wildtype and TAp73 knockout mice Less...