Lu Kevin L, Yamashita Yukiko M
Life Sciences Institute, University of Michigan, Ann Arbor, United States.
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.
Elife. 2017 Aug 15;6:e27960. doi: 10.7554/eLife.27960.
Two broadly known characteristics of germ cells in many organisms are their development as a 'cyst' of interconnected cells and their high sensitivity to DNA damage. Here we provide evidence that in the testis, connectivity serves as a mechanism that confers to spermatogonia a high sensitivity to DNA damage. We show that all spermatogonia within a cyst die synchronously even when only a subset of them exhibit detectable DNA damage. Mutants of the fusome, an organelle that is known to facilitate intracyst communication, compromise synchronous spermatogonial death and reduces overall germ cell death. Our data indicate that a death-promoting signal is shared within the cyst, leading to death of the entire cyst. Taken together, we propose that intercellular connectivity supported by the fusome uniquely increases the sensitivity of the germline to DNA damage, thereby protecting the integrity of gamete genomes that are passed on to the next generation.
在许多生物体中，生殖细胞有两个广为人知的特征：它们作为相互连接的细胞“囊肿”发育，以及对DNA损伤高度敏感。在这里，我们提供证据表明，在睾丸中，细胞连接作为一种机制，赋予精原细胞对DNA损伤的高度敏感性。我们发现，即使囊肿内只有一部分精原细胞表现出可检测到的DNA损伤，囊肿内的所有精原细胞也会同步死亡。已知促进囊肿内细胞间通讯的细胞器——融合体的突变体，会损害精原细胞的同步死亡，并减少整体生殖细胞死亡。我们的数据表明，促死亡信号在囊肿内共享，导致整个囊肿死亡。综上所述，我们提出，由融合体支持的细胞间连接独特地增加了种系对DNA损伤的敏感性，从而保护传递给下一代的配子基因组的完整性。
