Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America.
PLoS One. 2013 Aug 5;8(8):e70678. doi: 10.1371/journal.pone.0070678. Print 2013.
Tissue replenishment from stem cells follows a precise cascade of events, during which stem cell daughters first proliferate by mitotic transit amplifying divisions and then enter terminal differentiation. Here we address how stem cell daughters are guided through the early steps of development. In Drosophila testes, somatic cyst cells enclose the proliferating and differentiating germline cells and the units of germline and surrounding cyst cells are commonly referred to as cysts. By characterizing flies with reduced or increased Epidermal Growth Factor (EGF) signaling we show that EGF triggers different responses in the cysts dependent on its dose. In addition to the previously reported requirement for EGF signaling in cyst formation, a low dose of EGF signaling is required for the progression of the germline cells through transit amplifying divisions, and a high dose of EGF signaling promotes terminal differentiation. Terminal differentiation was promoted in testes expressing a constitutively active EGF Receptor (EGFR) and in testes expressing both a secreted EGF and the EGFR in the cyst cells, but not in testes expressing either only EGF or only EGFR. We propose that as the cysts develop, a temporal signature of EGF signaling is created by the coordinated increase of both the production of active ligands by the germline cells and the amount of available receptor molecules on the cyst cells.
干细胞通过一系列精确的级联事件进行组织补充，在此过程中，干细胞后代首先通过有丝分裂过渡扩增分裂进行增殖，然后进入终末分化。在这里，我们探讨了干细胞后代如何在早期发育过程中得到指导。在果蝇的睾丸中，体腔细胞包围着增殖和分化的生殖细胞，生殖细胞和周围体腔细胞的单位通常被称为小囊。通过对表皮生长因子（EGF）信号转导减少或增加的果蝇进行特征描述，我们发现 EGF 根据其剂量在小囊中触发不同的反应。除了之前报道的 EGF 信号转导在小囊形成中的要求外，低剂量的 EGF 信号转导对于生殖细胞通过过渡扩增分裂的进展是必需的，而高剂量的 EGF 信号转导促进终末分化。在表达组成性激活的表皮生长因子受体（EGFR）的睾丸中和在表达生殖细胞分泌的 EGF 和 EGFR 的体腔细胞中的睾丸中促进了终末分化，但在仅表达 EGF 或仅表达 EGFR 的睾丸中没有促进终末分化。我们提出，随着小囊的发育，生殖细胞产生的活性配体数量的协调增加以及体腔细胞上可用受体分子的数量，EGF 信号产生了一个时间特征。
