Fig. 5.

Role of TAp73 in germ cell maturation. Germ cells (gray cells) mature in pockets of somatic Sertoli cells (large pink cell). This requires the cyclical disassembly and reassembly of blood testis barrier (BTB) and Sertoli–germ cell junctions to allow the upward migration of germ cells on their maturational journey to the tubular lumen. TAp73 is exclusively produced in germ cells and controls a balanced transcriptional program that mediates adhesion to and disadhesion from Sertoli cell pockets, which includes peptidase inhibitors (Timps, Serpins), proteases (MMP, matrix metalloproteinases; PA, plasminogen activator-type serine proteases), receptors and integrins, thereby ensuring germ cell maturation. Upon TAp73 loss, there is broad dysregulation of these adhesion and migration effectors. This leads to junctional defects (adherens junctions, ectoplasmic specialization) and defective BTB with secondary degeneration of Sertoli cells. The end result is a massive loss of immature germ cells (spermatocytes, round and elongated spermatids) and mature spermatozoa, causing impaired fertility.