並列タイトル等ショウジョウバエの発生におけるリピンおよびセロトニントランスポーターの新規機能に関する研究
一般注記type:Thesis
Lipin and Serotonin transporter (SerT) are two highly conservative proteins in both human and Drosophila, which are well-known for their regular function. Lipin takes part in the mobilization of stored lipids to generate energy when the body requires. SerT, on the other hand, plays an important role in regulating Serotonin levels ? a vital neurotransmitter, responsible for multiple psychological activities in the central nervous system (CNS). Since lipin and SerT can be found in various kind of tissue in a living organism, not only in fat body or CNS for their respective roles, I suspect there are several functions of lipin and SerT remain unknown. In this thesis, I discuss novel roles of lipin and SerT in development using Drosophila model. First, I can visualize the expression of lipin in the wing disc and knockdown of this gene disrupt normal wing pattern formation. Knockdown of lipin in the 3rd instar larvae wing disc induces DNA damage. DNA damage, in turn, initializes the G2/M DNA damage checkpoint by down-regulating cyclin B expression, which then prevents the cell cycle transition from S-phase to M-phase. Additionally, the dysfunction of lipin induces cells to undergo apoptosis, leading to the formation of wing notching with a significantly smaller size. Next, SerT highly expresses in Drosophila eye discs and knockdown of SerT gene leads to a combination of rough and bald eye phenotype. SerT knockdown down-regulate the activation of the PI3K/Akt pathway, which induces excessive cell death in this tissue and in turn activates the compensatory proliferation mechanism to accumulating massive cluster of proliferating cells in the posterior region of the eye disc. This chain process induces the elevated recruitment of DNA in cone cells nuclei, impairs cone cells normal formation, and leads to rough phenotype. Taken together, these results suggest novel links of an energy-related protein (lipin) and psychological-related protein (SerT) in development.
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受理日（W3CDTF）2024-02-02T16:16:38+09:00
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