Mystery of Blood-Testis Barrier -how do germ cells pass through it?

 

Seiji Takashima^1,2,3,4

 

¹Department of Applied Biology, Faculty of Textile Science and Technology,

²Department of Textile Science and Technology, Interdisciplinary Graduate School of Science and Technology,

³Department of Biotechnology, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research,

⁴Shinshu Sustainability Transformation Initiative, Shinshu University.

 

Spermatogonial stem cells (SSCs) are the foundation for life-long spermatogenesis in mammals. And their niche cyclically produces several factors to achieve both maintenance of SSC number and differentiation of germ cells at each maturity grade. Simultaneously, Sertoli cells, one of the major components of the SSC niche, construct a tight junction band/zonula occludens called Blood-Testis Barrier (BTB). Since the defect in BTB (e.g. CLDN11 deficiency) results in spermatogenic arrest at the post-meiotic stage, it is a classical belief that BTB is one of the essential elements of SSC niche for proper spermatogenesis. Our previous study demonstrated that CLDN3 expression induced by activated RAC1 is indispensable for transplanted SSCs to pass through BTB. And our team is now tackling to understand how BTB is regulated to allow differentiating germ cells to pass through it without compromising barrier function. In this talk, I would like to show the recent advance in the regulation of BTB, focusing on our finding that a membrane glycolipid on meiotic germ cells is essential for the barrier function of BTB.

 

Related references

1. Kanatsu-Shinohara, M., Takehashi, M., Takashima, S., Lee, J., Morimoto, H., Chuma, S., Raducanu, A., Nakatsuji, N., Fässler, R., Shinohara, T. Homing of mouse spermatogonia stem cells to germline niche depends on beta1-integrin. Cell Stem Cell 3, 533-542, 2008.
2. Takashima, S., Kanatsu-Shinohara, M., Tanaka, T., Takehashi, M., Morimoto, H., Shinohara, T. Rac mediates mouse spermatogonial stem cell homing to germline niches by regulating transmigration through the blood-testis barrier. Cell Stem Cell 9, 463-475, 2011.
3. Kanatsu-Shinohara, M., Inoue, K., Takashima, S., Takehashi, M., Ogonuki, N., Morimoto, H., Nagasawa, T., Ogura, A., Shinohara T. Reconstitution of mouse spermatogonial stem cell niches in culture. Cell Stem Cell 11, 567-578, 2012.
4. Mori, Y., Takashima, S., Kanatsu-Shinohara, M., Yi, Z., Shinohara, T. Cdc42 is required for male germline niche development in mice. Cell Rep. 36, 109550, 2021.