LHX2 in germ cells control tubular organization in the developing mouse testis

Abstract

AbstractIn 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,Lhx2is expressed in the germ cells of the developing testis between E12.5-E15.5. InLhx2knockout-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 ofLhx2led to disrupted endothelial cell migration and expansion of interstitial cells in the XY gonads. The cords in the developing testis ofLhx2knockout embryos are disorganized with a disrupted basement membrane. Together, our results show an important role ofLhx2in testicular development and imply the involvement of germ cells in the tubular organization of the differentiating testis.HighlightLhx2is expressed in germ cells of developing mouse testis but is dispensable for germ cell and Sertoli cell specificationLoss ofLhx2disrupts testicular vascularization, leads to the expansion of interstitial cells, and alters the tubular organizationGerm cells govern the tubular organization in the developing testisGraphical Abstract