LHX2 in Germ Cells Control Tubular Organization in the Developing Mouse Testis

In the gonads of mammalian XY embryos, the organization of cords is the hallmark of testis development. This organization is thought to be controlled by interactions of the Sertoli cells, endothelial and interstitial cells with little or no role of germ cells. Challenging this notion, herein we show that the germ cells play an active role in the organization of the testicular tubules. We observed that the LIM-homeobox gene, Lhx2 is expressed in the germ cells of the developing testis between E12.5-E15.5. In Lhx2 knockout-fetal testis there was altered expression of several genes not just in germ cells but also in the supporting (Sertoli) cells, endothelial cells, and interstitial cells. Further, loss of Lhx2 led to disrupted endothelial cell migration and expansion of interstitial cells in the XY gonads. The cords in the developing testis of Lhx2 knockout embryos are disorganized with a disrupted basement membrane. Together, our results show an important role of Lhx2 in testicular development and imply the involvement of germ cells in the tubular organization of the differentiating testis. The preprint version of this manuscript is available at https://doi.org/10.1101/2022.12.29.522214