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. Author manuscript; available in PMC: 2016 Nov 13.
Published in final edited form as: Annu Rev Cell Dev Biol. 2015 Sep 3;31:291–315. doi: 10.1146/annurev-cellbio-100913-013344

Figure 3.

Figure 3

The architecture and signaling of the mammalian testis niche. (a) The seminiferous tubule is bounded by a basement membrane, which separates the site of spermatogenesis from the interstitial space, where Leydig cells, myoid cells, and macrophages reside. Quiescent, somatic Sertoli cells adhere to the basal lamina but extend long cytoplasmic processes toward the tubule lumen, simultaneously contacting thousands of germ cells at all stages of differentiation. Sertoli cells meet at specialized tight junctions that comprise the blood-testis barrier (BTB) and polarize the seminiferous epithelium into basal and adluminal compartments (Oatley & Brinster 2012). Spermatogonial stem cells (SSCs) and spermatogonia reside in a single layer on the basement membrane of the seminiferous tubule, where they divide with incomplete cytokinesis to form interconnected clusters of germ cells. As germ cells differentiate, they move toward the tubule lumen. (b) Systemic gonadotropin follicle-stimulating hormone (FSH) regulates the secretion of the glial cell line–derived neurotrophic factor (GDNF) from Sertoli cells. This ligand, along with the secretion of fibroblast growth factor 2 (FGF2) from Sertoli cells, activates the phosphatidylinositol 3-kinase–Akt (PI3K-Akt) and Mitogen-activated protein kinase (MAPK) signaling pathways in SSCs and their daughters. Both pathways in turn upregulate the transcription factors ETS variant 5 (Etv5) and B-cell CLL/lymphoma 6 member B (Bcl6b), which are necessary for SSC self-renewal, though GDNF alone induces POU domain class 3 transcription factor 1 (Oct6) expression (Oatley et al. 2006, Wu et al. 2010, Ishii et al. 2012). Zinc finger and BTB domain containing 16 (Plzf) is another important transcription factor required for SSC self-renewal, but what regulates its expression is unknown (Buaas et al. 2004, Costoya et al. 2004). Colony stimulating factor 1 (CSF1) is secreted from both Leydig and myoid cells and is thought to regulate maintenance specifically in the stem cells (Oatley et al. 2009).