Chapter 15 - Transcription Factors in Sertoli Cells
Publisher Summary
This chapter discusses the role of transcription factors in regulating Sertoli cell-specific gene expression. Transcription factors are DNA binding proteins (trans-acting) that bind to DNA regulatory elements located cis to the target genes. Transcription factors are generally considered final targets of signal-transduction pathways. The level of expression of transcription factors and their activities determines whether their target genes are transcribed and to what extent. These regulators of gene expression in turn are tightly regulated by a multitude of signaling pathways influenced by cell–cell interaction, growth factors, hormones, extracellular matrix, and the stage of development. Alterations in the transcriptional regulation of the Sertoli cell determine changes in cellular differentiation and function. The functional and developmental changes associated with Sertoli cell differentiation and functions are a result of stage-specific activation/repression of specific transcription factors. Some of these transcription factors such as Sry and DAX-1are expressed only during a particular stage of development.
References (0)
Cited by (1)
Krüppel-like factor 4 is involved in functional differentiation of testicular Sertoli cells
2008, Developmental BiologyKrüppel-like factor 4 (KLF4) is a pleiotropic zinc finger transcription factor that regulates genes being involved in differentiation and cell-cycle control. Knockout studies revealed a critical function for KLF4 in the terminal differentiation of many epithelial cells. In testicular Sertoli cells, Klf4 is strongly inducible by the glycoprotein follicle stimulating hormone (FSH). Because KLF4 is essential for postnatal survival in mice, we deleted Klf4 specifically in Sertoli cells using the Cre/loxP system. Importantly, around postnatal day 18, a critical period of terminal Sertoli cell differentiation, mutant seminiferous tubules exhibited a disorganized germinal epithelium and delayed lumen formation. The ultrastructural finding of highly vacuolized Sertoli cell cytoplasm and the identification of differentially expressed genes, which are known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggest impaired apical secretion of the Sertoli cell. Interestingly, a high proportion of all identified genes was localized in a small subregion of chromosome 7, suggesting coordinated regulation. Intriguingly, adult mutant mice are fertile and show normal testicular morphology, although the testosterone levels are decreased. In summary, KLF4 plays a significant role for proper and timely Sertoli cell differentiation in pubertal mice.