Institute of Biology-Cytogenetics, Humboldt University Berlin, 10115 Berlin, Germany.
Genetics. 2010 Mar;184(3):731-44. doi: 10.1534/genetics.109.109967. Epub 2009 Dec 14.
Coordinating cell proliferation and differentiation is essential during organogenesis. In Drosophila, the photoreceptor, pigment, and support cells of the eye are specified in an orchestrated wave as the morphogenetic furrow passes across the eye imaginal disc. Cells anterior of the furrow are not yet differentiated and remain mitotically active, while most cells in the furrow arrest at G(1) and adopt specific ommatidial fates. We used microarray expression analysis to monitor changes in transcription at the furrow and identified genes whose expression correlates with either proliferation or fate specification. Some of these are members of the Polycomb and Trithorax families that encode epigenetic regulators. Osa is one; it associates with components of the Drosophila SWI/SNF chromatin-remodeling complex. Our studies of this Trithorax factor in eye development implicate Osa as a regulator of the cell cycle: Osa overexpression caused a small-eye phenotype, a reduced number of M- and S-phase cells in eye imaginal discs, and a delay in morphogenetic furrow progression. In addition, we present evidence that Osa interacts genetically and biochemically with CyclinE. Our results suggest a dual mechanism of Osa function in transcriptional regulation and cell cycle control.
协调细胞增殖和分化是器官发生过程中的关键。在果蝇中,感光细胞、色素细胞和眼部支持细胞在形态发生沟穿过眼盘时,以协调的波的形式被特化。在沟的前面的细胞尚未分化,仍然处于有丝分裂活跃状态,而在沟中的大多数细胞在 G1 期停滞,并采用特定的小眼命运。我们使用微阵列表达分析来监测沟处的转录变化,并鉴定了与增殖或命运特化相关的表达变化的基因。其中一些是 Polycomb 和 Trithorax 家族的成员,它们编码表观遗传调节剂。Osa 就是其中之一;它与果蝇 SWI/SNF 染色质重塑复合物的成分相关。我们对 Osa 在眼部发育中的研究表明,它是细胞周期的一个调节因子:Osa 的过表达导致小眼表型、眼盘的 M 和 S 期细胞数量减少以及形态发生沟进展的延迟。此外,我们还提供了证据表明,Osa 在遗传和生化上与 CyclinE 相互作用。我们的结果表明,Osa 在转录调控和细胞周期控制中的功能具有双重机制。