Retinoic acid signaling in Sertoli cells regulates organization of the blood-testis barrier through cyclical changes in gene expression

  • Kazuteru Hasegawa
    Division of Mammalian Development, National institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan
  • Yumiko Saga
    Division of Mammalian Development, National institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan

説明

<jats:p>Mammalian spermatogenesis contributes a constant production of large numbers of spermatozoa, which is achieved by a cyclically regulated program known as the seminiferous epithelial cycle. Sertoli cells, functionally unique somatic cells, create a microenvironment to support the continuous differentiation of germ cells especially through the formation of a blood-testis barrier (BTB). The BTB is essential for maintaining homeostasis in seminiferous tubules and opens transiently at stages VII-VIII to ensure constant differentiation of spermatogenic cells. However, it is poorly understood how the dynamic organization of BTB is regulated. In our current study, we find that the overexpression of a dominant-negative form of RARα (dnRARα) in Sertoli cells disrupts the BTB at stages VII-XII and causes the large-scale apoptosis of differentiating germ cells. These abnormal events are found to be associated with cyclical gene expression changes in Sertoli cells, which can be represented by abnormal activation and repression of genes showing peaks of expression during stages I-VI and VII-XII, respectively. We find that one such gene, Ocln, encoding a tight junction component, partly contributes to the BTB disruption caused by dnRARα. Taken together, our data suggest that the cyclical activation of RA signaling in Sertoli cells during stages VII-XII contributes to a periodic organization of the BTB through changes in stage-dependent gene expression.</jats:p>

収録刊行物

  • Development

    Development 139 (23), 4347-4355, 2012-12-01

    The Company of Biologists

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