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In many cell types, the process of differentiation is linked to the cessation of proliferation and the inactivation of retinoblastoma protein (RB). In this issue of Molecular Endocrinology, Nalam et al. investigate a conditional knockout of RB in Sertoli cells, the somatic support cells of the seminiferous tubules. In addition to cell cycle and apoptotic defects related to aberrant activation of the E2F pathway, mutant Sertoli cells show profound defects in differentiation both related and unrelated to abnormal regulation of androgen receptor (AR)-responsive genes. Biotin tracer studies showed that unlike the control (top right), mutant testes (bottom left) had pervasive biotin staining (red) throughout the tubule, suggesting dysfunctional blood-testis barrier function. Espin staining (green) showed a lack oforganization of actin-rich structures both in the basal and apical compartments of the seminiferous tubules. From the article in this issue by Nalam et al., pages 1900–1913.

The editors thank Dr. Ron Smith, Alcon Laboratories, Fort Worth, TX, for collaborating with the authors to create the figure on the cover.