Paraspeckle 是一個位於真核生物細胞核內染色質間的斑點狀結構，由一條長鏈
非編碼核糖核酸 NEAT1 和 DBHS 家族蛋白和其他核糖核酸所組成。先前研究發現
paraspeckle 為一個受細胞刺激調控的動態結構。DBHS 家族蛋白在脊椎動物中包
括 PSPC1、SFPQ 和 NONO 三個成員，他們參與基因調控、核糖核酸加工和運輸，
以及去氧核醣核酸的修復等。PSPC1 不只是 paraspeckle 上的結構蛋白，還是一個
新發現的共轉錄因子，然而目前對於 PSPC1 在發育當中的角色仍然未知。由於斑
馬魚生命週期短、生長速度快、透明方便觀察等優勢，我們利用斑馬魚胚胎來研究
pspc1 在發育中的功能。首先，我們觀察到 pspc1 在自幼魚時期到成年期的表現集
中在頭部和腦的區域。透過顯微注射實驗於胚胎中改變 pspc1 的表現量，利用
CRISPR/Cas9 系統或嗎啉基的基因敲落技術，發現卵黃包覆過程的延遲，和受精後
一天大的幼魚有著彎曲的尾鰭、卵黃囊水腫、U 形體節、心包膜積水等異常發育，
或更嚴重的軀幹喪失。而過度表達 pspc1 則會破壞幼魚的大腦和軀幹形成。為了進
一步了解 pspc1 是否透過影響神經脊細胞參與大腦形成或神經發育，我們利用帶有
sox10 一種神經脊細胞標誌物發綠螢光的基因轉殖魚胚胎，過表達 PSPC1 後三天
大的幼魚有頜軟骨異常和較小的眼睛。以上的結果顯示 pspc1 在斑馬魚的早期胚胎
發育中扮演重要的角色，而我們的研究有助於更多的了解對於 pspc1 在正常生理條
件下在動物發育中的作用。

Paraspeckle is a small, spotted-shaped subnuclear body composed of a long non-coding RNA, the core Drosophila behavior/human splicing (DBHS) family proteins, and other RNAs. It has been reported as a dynamic structure responsive to cellular stress. The DBHS family members, including Paraspeckle component 1 (PSPC1), non-POU domaincontaining octamer-binding protein (NONO) and splicing factor, proline- and glutaminerich (SFPQ) in vertebrates, are involved in gene regulation, RNA processing and transport, and DNA repair. PSPC1 is not only a paraspeckle structural protein but also a novel cotranscription factor. However, the role of PSPC1 in development remains unknown. Due to the advantage of the fast growth of zebrafish and the transparent developing embryos, we employed zebrafish embryos to investigate how pspc1 functions in zebrafish embryo development. We found that the pspc1 was specifically expressed in the head and brain region one day postfertilization (dpf), and the expression was sustained throughout the larvalstage and adulthood. Knockdown of pspc1 expression in embryos by CRISPR/Cas9 system or morpholino showed developmentally delayed phenotype during epiboly, and abnormal development such as the curved tail, yolk sac edema, U-shaped somites, pericardial effusion, and more severe phenotype such as loss of trunk in 1 dpf larvae. Moreover, overexpressing pspc1 disrupted the brain and trunk formation in 1 dpf larvae. To further examine whether pspc1 contributes to brain formation or neurogenesis by regulating neural crest cells (NCCs), we employed the embryos of Tg(sox10:eGFP), a neural crest cell marker. Overexpressing human PSPC1 (hPSPC1) in Tg(sox10:eGFP) embryos led to jaw cartilage anomaly and smaller eye size in 3 dpf larvae. Our results indicated that pspc1 may play an important role in zebrafish embryo development. Taken together, our studies help us to understand more about the function of pspc1 under normal physiology in animal development.

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