Bertho Sylvain, Clapp Mara, Banisch Torsten U, Bandemer Jan, Raz Erez, Marlow Florence L
Department of Cell, Developmental and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1020 New York, NY 10029-6574, USA.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Development. 2021 Apr 1;148(7). doi: 10.1242/dev.187773. Epub 2021 Apr 15.
Fertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionarily conserved process involves synchronous and incomplete mitotic divisions of a GC daughter (cystoblast) to generate sister cells connected by intercellular bridges that facilitate the exchange of materials to support rapid expansion of the gamete progenitor population. Here, we investigated cystogenesis in zebrafish and found that early GCs are connected by ring canals, and show that Deleted in azoospermia-like (Dazl), a conserved vertebrate RNA-binding protein (Rbp), is a regulator of this process. Analysis of dazl mutants revealed the essential role of Dazl in regulating incomplete cytokinesis, germline cyst formation and germline stem cell specification before the meiotic transition. Accordingly, dazl mutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry, dazl is required for germline stem cell establishment and fertility.
生殖系干细胞的不对称分裂可维持生育能力和配子储备，从而产生新的干细胞或分化为配子的子代细胞。在进入减数分裂之前，有性动物的分化生殖细胞（GCs）通常会经历包囊形成过程。这一进化上保守的过程涉及GC子代细胞（成囊母细胞）的同步且不完全有丝分裂，以产生通过细胞间桥连接的姐妹细胞，这些细胞间桥有助于物质交换，以支持配子祖细胞群体的快速扩增。在此，我们研究了斑马鱼中的包囊形成过程，发现早期GCs通过环形通道相连，并表明类无精子症缺失蛋白（Dazl），一种保守的脊椎动物RNA结合蛋白（Rbp），是这一过程的调节因子。对dazl突变体的分析揭示了Dazl在减数分裂转变前调节不完全胞质分裂、生殖系包囊形成和生殖系干细胞特化中的重要作用。因此，dazl突变体的GCs形成有缺陷的环形通道，并最终保持为未能分化为减数分裂细胞的单个细胞。除了促进成囊母细胞分裂和减数分裂进入外，dazl对于生殖系干细胞的建立和生育能力也是必需的。
