GATA4 IS REQUIRED FOR TESTICULAR DEVELOPMENT
Cell and Molecular Biology
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Sex differentiation occurs at embryonic day 10.5 (E10.5) in the mouse. In the XY mouse embryos, appearance of testis cords at E11.5 marks the onset of testis formation. The primary testis cords subsequently undergo further development characterized by rapid and extensive branching, elongation and coiling, resulting in hundreds of thousands of secondary or tertiary testis cords, which will develop into future seminiferous tubules during postnatal testicular development. Here we report that inactivation of Gata4 at E12.5 in Sertoli cells does not affect testis cord formation, but blocks its further development leading to testicular dysgenesis and male infertility in adult mice. Our data demonstrate that Gata4 is required for normal testis cord branching, elongation during embryonic development, and untimely the normal number of seminiferous tubule precursors available for the postnatal testicular development. Disruption of Gata4 or its target genes involved in testis cord development will significantly affect the number of future seminiferous tubules, the size of the testis and fertility.