Castor is required for Hedgehog-dependent cell-fate specification and follicle stem cell maintenance in Drosophila oogenesis
Castor is required for Hedgehog-dependent cell-fate specification and follicle stem cell maintenance in Drosophila oogenesis
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DOI：
10.1073/pnas.1300725110
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发表时间：
2013-05-07
影响因子：
11.1
通讯作者：
Montell, Denise J.
中科院分区：
文献类型：
--
作者：
Chang, Yu-Chiuan;Jang, Anna C. -C.;Montell, Denise J.
干细胞的不对称分裂导致子细胞的自我更新和分化。了解从成体组织干细胞分化特定细胞类型的分子和机制是发育生物学和再生医学的主要挑战。果蝇卵泡干细胞（FSC）是研究成体干细胞行为的一个很好的模型系统，然而，卵泡细胞分化的最早阶段仍然很神秘。在这里，我们将Castor（Cas）确定为一种核蛋白，它在FSC和早期滤泡细胞前体中表达，然后在卵室形成后仅限于分化的极细胞和柄细胞。Cas是FSC维持和极性和柄细胞命运规格所必需的。眼缺失（Eya）被排除在极细胞和柄细胞之外，并通过抑制Cas表达来抑制它们的命运。Hedgehog信号传导对于抑制Eya以允许Cas在极细胞和柄细胞中表达是必不可少的。最后，我们发现，Cas和Eya的互补模式揭示了极性和柄前体细胞在其发展的最早阶段逐渐分化。我们的研究提供了一个标记细胞的命运，在这个模型和洞察的分子和细胞机制，FSC后代分化成不同的命运。
Asymmetric division of stem cells results in both self-renewal and differentiation of daughters. Understanding the molecules and mechanisms that govern differentiation of specific cell types from adult tissue stem cells is a major challenge in developmental biology and regenerative medicine. Drosophila follicle stem cells (FSCs) represent an excellent model system to study adult stem cell behavior; however, the earliest stages of follicle cell differentiation remain largely mysterious. Here we identify Castor (Cas) as a nuclear protein that is expressed in FSCs and early follicle cell precursors and then is restricted to differentiated polar and stalk cells once egg chambers form. Cas is required for FSC maintenance and polar and stalk cell fate specification. Eyes absent (Eya) is excluded from polar and stalk cells and represses their fate by inhibiting Cas expression. Hedgehog signaling is essential to repress Eya to allow Cas expression in polar and stalk cells. Finally, we show that the complementary patterns of Cas and Eya reveal the gradual differentiation of polar and stalk precursor cells at the earliest stages of their development. Our studies provide a marker for cell fates in this model and insight into the molecular and cellular mechanisms by which FSC progeny diverge into distinct fates.