在這個研究中，我們試著去瞭解兩個與Notch相關基因(mib與nicastrin)在斑馬魚早期發育中所扮演的角色。在mib的研究中，我們採用mibnn2002來作為研究材料。因為它具有過去mib突變種所沒有的特殊性狀。這樣的性狀讓我們有機會瞭解mib未知的功能。然而，我們發現這個突變種有一個9.6 Mbp大小的基因片段缺失，其中包含了foxc1a與mib基因。mib基因的遺失導致其呈現與mibtfi91相似的分子性狀，包含her4表現量下降、神經元細胞些微增加以及冷敏感性的dlc同步表現異常。雖然在這個研究中，我們沒有藉由研究此突變種的特殊性狀找到mib的新功能，我們卻發現了foxc1a只在早期肌節特化上是必要的，較晚生成的肌節則不用，這點發現修正了早先對foxc1a在肌節特化上功能上的結論(過去認為foxc1a基因是早期跟晚期的肌節發育皆必要的基因)。這個發現也與新近由foxc1a變異種研究所得的結論吻合，該研究發現foxc1a基因是早期的肌節發育所必需的。而在nicastrin的研究中，我們發現在胚胎黑色素細胞中，γ-secretase需要Nicastrin來執行它的功能。當nicastrin的mRNA缺乏時，會導致黑色素細胞死亡，視網膜色素上皮退化與視覺感光細胞退化。我們發現黑色素小體在黑色素細胞中的成熟需要nicastrin。 我們猜測不成熟的黑色素小體中的Tyrosinase下游產物，可能會導致我們觀察到的粒線體結構異常與黑色素細胞壞死。利用藥物抑制Tyrosinase，其結果也支持這樣的想法。除了黑色素細胞外，我們也發現自由基抑制藥物，在存在視網膜色素上皮的情況下，可以在一定程度上緩解視覺感光細胞在nicastrin突變種中的退化現象。簡要來說，我們發現foxc1a的表現是mibnn2002突變種早期的肌節特化需要的，但其表現與否並不影響mibnn2002突變種晚期的肌節特化；黑色素細胞中的黑色素小體成熟需要nicastrin的表現。缺乏nicastrin會導致黑色素細胞產生Tyrosinase介導的粒線體腫脹與黑色素細胞壞死。

Here, we examined the function of two Notch related genes, mib and nicastrin, in zebrafish early development. In the study of mib, its function was studied by the mibnn2002 mutant, which showed distinct phenotypes from previous mib mutants and might reveal novel function of mib. However, a 9.6 Mbp chromosome deletion was found in mibnn2002, which includes foxc1a and mib. The deletion of mib results in the down-regulation of her4, neuronal cell slighly increase and cold sensitive dlc synchronization defect which mimics the molecular phenotypes of mibtfi91. Although we did not identify a new function of mib through studying its distinct phenotypes, we found that foxc1a is only required for the specification of early somites, but not later somites. The finding rectifies previous conclusion, which suggests that foxc1a is required for not only early somitogenesis but also late somitogenesis. This finding is also echoed by a recent report, which showed that foxc1a is required for early somitogenesis. In the study of nicastrin, we found that Nicastrin is required for the function of γ-secretase in the embryonic melanocytes. The deficiency of nicastrin transcript could lead to depigmentation, retinal pigment epithelium degeneration and photoreceptor degeneration. nicastrin was found to be required for the maturation of melanosomes in the melanocytes. Mitochondria malformation and melanocyte necrosis were suppressed by the treatment of Tyrosinase inhibitor. In contrast to melanocytes, ROS inhibitor, in addition to the existence of RPE, was required to partially rescue the photoreceptors in the nicastrin mutant. In short, we found that the expression of foxc1a in the PSM is only required for early somite specification, but not late somite specification in the mibnn2002 mutant; The expression of nicastrin is required for melanosome maturation in the melanocytes. The deficient of nicastrin transcript in the melanocyte could lead to Tyrosinase mediated mitochondria swelling and cell necrosis.

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