Wing morphogenesis defect (wmd)在果蠅發育中所扮演的角色

The role of wing morphogenesis defect (wmd) during Drosophila oogenesis

林佩誼(Lin, Pei Yi)

指導教授 ： 徐瑞洲

國立清華大學/生命科學院/分子醫學研究所/碩士(2014年)

https://doi.org/10.6843/NTHU.2014.00187

摘要

wing morphogenesis defect (wmd)是一個具有七個WD-40 repeats 蛋白，在過去研究中已知會當成scaffold蛋白，和許多蛋白形成蛋白間有相互作用，參與細胞內調控訊號傳遞。Wmd為果蠅Serine-Threonine kinase Receptor-Associated Protein （STRAP）同源性分子，在過去研究STRAP哺乳動物的實驗中證實會參與調控Transforming Growth Factor-β(TGF-β)訊號傳遞中。而在果蠅翅膀發育中篩選參與調控EGFR和TGFF-β訊息的下游分子，Wmd是其中一個被篩選出的分子，因有果蠅翅膀發育上型態缺失因而命名為wing morphogenesis defect (wmd)。在此篇論文中我們利用成蟲母果蠅卵母細胞發育為模式生物，探討分析Wmd突變時所造成的影響。維持卵母細胞的發育是透過細胞骨架微管運送營養物質;類似的機制我們也在果蠅幼蟲複眼的單層表皮細胞中，成熟感光神經細胞中，核的移動得到相似的對應。我們發現wmd突變細胞內，沒有卵母細胞（oocyte）生成，細胞命運已被取代成營養細胞（nurse cell）。兩種細胞之間的不同在於卵母細胞會有特定的蛋白，例如：Egl，Bic-D，Orb累積以維持卵母細胞的成長。而特定蛋白的累積則是透過細胞骨架微管（microtubule）當成運送橋樑從營養細胞穿過細胞間通道（ring canals）運送到卵母細胞。相似的機制在感光神經細胞發育中，成熟的神經細胞核會從細胞基部往頂部移動也是透過細胞骨架微管運送;我們觀察到wmd突變細胞內，感光神經細胞沒有往頂部移動，更甚至往基部視柄移位的現象。在過去的研究中認為Wmd屬於MAPs (Microtubule Associated Protein)，而我們證實Wmd會直接與微管（microtubule）結合也會和EB1 (microtubule end plus binding 1)結合。因此我們認為Wmd是利用其七個WD-40片段當成scaffold蛋白與微管（microtubule），和EB1結合，形成MAPs與蛋白之間相互作用，因而調控微管的穩定度，藉此而影響卵母細胞特定蛋白和感光神經細胞核的運送。

關鍵字

wing morphogenesis defect (wmd)

並列摘要

wing morphogenesis defect (wmd) encodes a WD-40 domain-containing protein that plays critical roles in shaping wing morphology. Wmd shows significant homology with mammalian serine-threonine kinase receptor-associated protein (STRAP) that regulates transforming growth factor-β (TGF-s) signaling. WD-40 domain mediates diverse protein-protein interactions, including those involved in scaffolding and the cooperative assembly and regulation of dynamic multi-subunit complexes. We characterize the function of wmd during Drosophila development. Our results indicate that Wmd is involved in both oocyte determination during oogenesis and nuclear positioning in the developing photoreceptors. The progressive establishment of oocyte fate and nuclear positioning relies on microtubule-dependent. The microtubule network is thought to provide the basic intracellular framework for motility, while dynein and dynactin contribute motor activity and several mRNAs such as Bic-D, egl, orb and Dhc begin to accumulate in the oocyte. Disruption of microtubules results in a block in oocyte determination and nuclear migration. Previously studied, Wmd was shown to be a member of microtubule-associated proteins via a MT cosedimentation assay. These support the notion that Wmd functions with the microtubules to regulate nuclear migration. We show that germline clones of the wmd give rise to 16 nurse cell cysts, and we have analysed this phenotype using a variety of oocyte markers to investigate the role of Wmd in oocyte determination. Here we show that the Wmd acts together with microtubules and EB1 to stabilize microtubules to determine oocyte identity and required for nuclear localization in developing nervous system.

並列關鍵字

wing morphogenesis defect (wmd)

參考文獻

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