FGF9

Abstract: The "nurse cell" function of Sertoli cells in spermatogenesis was originally tacitly assumed on the basis of the anatomical relationships between cells in the testis. In mammals, from very early in prenatal development to the onset of meiosis and to the ultimate production of spermatozoa, the relationship between the germinal cells and the Sertoli cells is important and apparently obligatory. The experimental evidence supports the notion that the primary endocrine regulation of spermatogenesis via FSH and testosterone is manifested through actions on the Sertoli cells. Although diverse strategies are used by Sertoli cells to support germ cell development, one of the most important roles of Sertoli cells is the regulation of the intratubular and intercellular environment adluminal to the tight junctional complexes. The meiotic and post-meiotic germ cells are sequestered by Sertoli-Sertoli junctional complexes in an adluminal compartment that is isolated from the serum or lymph. As a result of this sequestering activity, the secretion products of the Sertoli cells and the meiotic germ cells determine the composition of this local environment that can influence meiosis as well as spermatid and spermatocyte development. Evidence is accumulating that paracrine and autocrine factors from Sertoli and germ cells are important in the functioning of both cell types. While it is important to know what Sertoli cells and germ cells make, it is equally important to know when they make it. Distinct but well-defined groups of germ cells interact with Sertoli cells in a cyclic pattern. These recurring groups of germ cells define the cycle of the seminiferous epithelium during which sperm are produced in an asynchronous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Recently, we demonstrated that loss of Fgf9 results in a block of testis development and a male to female sex-reversed phenotype; however, the function of Fgf9 in sex determination was unknown. We now show that Fgf9 is necessary for two steps of testis development just downstream of the male sex-determining gene, Sry: (1) for the proliferation of a population of cells that give rise to Sertoli progenitors; and (2) for the nuclear localization of an FGF receptor (FGFR2) in Sertoli cell precursors. The nuclear localization of FGFR2 coincides with the initiation of Sry expression and the nuclear localization of SOX9 during the early differentiation of Sertoli cells and the determination of male fate.

Abstract: GATA-1 is an essential factor for the transcriptional activation of erythroid-specific genes, and is also abundantly expressed in a discrete subset of cells bordering the seminiferous epithelium in tubules of the murine testis. In examining normal and germ-line defective mutant mice, we show here that GATA-1 is expressed only in the Sertoli cell lineage in mouse testis. GATA-1 expression in Sertoli cells is induced concomitantly with the first wave of spermatogenesis, and GATA-1-positive cells are uniformly distributed among all tubules during prepubertal testis development. However, the number of GATA-1-positive cells declines thereafter and were found only in the peripheral zone of seminiferous tubules in stages VII, VIII and IX of spermatogenesis in the adult mouse testis. In contrast, virtually every Sertoli cell in mutant W/Wv, jsd/jsd or cryptorchid mice (all of which lack significant numbers of germ cells) expresses GATA-1, thus showing that the expression of this transcription factor is negatively controlled by the maturing germ cells. These observations suggest that transcription factor GATA-1 is a developmental stage- and spermatogenic cycle-specific regulator of gene expression in Sertoli cells.