Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads
Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads
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DOI：
10.1073/pnas.1003462107
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发表时间：
2010-08-10
影响因子：
11.1
通讯作者：
Kobayashi, Satoru
中科院分区：
文献类型：
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作者：
Kitadate, Yu;Kobayashi, Satoru
生殖系干细胞 (GSC) 由体细胞微环境或 GSC 生态位维持，这确保 GSC 能够自我更新并产生功能性配子。然而，目前尚不清楚发育中性腺内如何调节适当的生态位大小和位置。在果蝇睾丸中，形成 GSC 生态位的中心细胞源自胚胎性腺前部的体细胞性腺前体 (SGP) 子集。在这里，我们表明 Notch 信号传导诱导中枢分化。雄性胚胎性腺中几乎所有SGPs中Notch均被激活，但后部SGPs中表皮生长因子受体（Egfr）被激活以抑制中枢分化，从而限制胚胎性腺中中枢分化的扩展。我们进一步表明，Egfr 在后 SGP 中被原始生殖细胞 (PGC) 分泌的 Spitz 配体激活，而 Notch 配体 Serrate 在 SGP 中表达。这表明改变 PGC 的数量会改变生态位大小。事实上，PGC 数量的减少会导致异位中枢分化，从而增加它们招募 PGC 作为 GSC 的机会。当异位中枢分化受到抑制时，数量减少的 PGC 无法转变为 GSC。因此，我们建议 SGP 通过从 PGC 到 SGP 的信号来感知 PGC 数量，从而调节生态位大小，并且这可以作为保护 GSC 的机制。
Germ-line stem cells (GSCs) are maintained by the somatic micro-environment, or GSC niche, which ensures that GSCs can both self-renew and produce functional gametes. However, it remains unclear how the proper niche size and location are regulated within the developing gonads. In the Drosophila testis, the hub cells that form the GSC niche are derived from a subset of somatic gonadal precursors (SGPs) in the anterior portion of the embryonic gonad. Here we show that Notch signaling induces hub differentiation. Notch is activated in almost all SGPs in the male embryonic gonad, but Epidermal growth factor receptor (Egfr) is activated in posterior SGPs to repress hub differentiation, thereby restricting the expansion of hub differentiation in the embryonic gonad. We further show that Egfr is activated in posterior SGPs by Spitz ligand secreted from primordial germ cells (PGCs), whereas the Notch ligand Serrate is expressed in SGPs. This suggests that varying the number of PGCs alters niche size. Indeed, a decrease in the number of PGCs causes ectopic hub differentiation, which consequently increases their opportunity to recruit PGCs as GSCs. When ectopic hub differentiation is repressed, the decreased number of PGCs fails to become GSCs. Thus, we propose that SGPs sense PGC number via signals from PGCs to SGPs that modulate niche size, and that this serves as a mechanism for securing GSCs.