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標題: Hedgehog 訊息對卵巢生殖幹細胞微環境(niche)形成所扮演的角色
Roles of Hedgehog Signaling for Ovarian Germline Stem Cell Niche Formation
作者: 賴俊銘
Chun-Ming Lai
關鍵字: 生殖幹細胞;微環境;細胞表面黏著特性;Germline Stem Cell;Niche;Cell adhesion
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Stem cells reside in different types of supporting cells, or niches, which fine-tune stem cell maintenance and differentiation in response to physiological demand. However, little is known about how those niches are formed. Here, we have used Drosophila ovary as model to study how germline stem cell (GSC) niches are formed during development. Firstly, we have identified that Hedgehog (Hh) signaling establishes precursors for GSC niches by regulating cell-cell adhesion. Mechanistically, Hh produced from forming terminal filament (TF) signals posteriorly for somatic gonadal precursors (SGPs) to specify stromal intermingle cells (ICs), which contributes to both adult GSC maintenance niche-cap cells and differentiation niche- escort cells, by suppressing E-cadherin expression. We also identified Traffic Jam (an orthologue of a large Maf transcription factor in mammals) is a novel transcriptional target of Hh signaling to control cell adhesion by negatively regulating E-cadherin. Interestingly, the determinant of ICs differentiates into cap cells requires down-regulation of Hh signaling, thereby E-cadherin is able to be expressed in cap cells for GSC recruitment. Furthermore, we identified that Delta produced from TFs activates Notch signaling in adjacent ICs, and results in suppression of Hh signaling via Cul3HIB/SPOP-mediated Ci degradation. Our results demonstrate that spatio-temporal regulation of Hh and Notch signaling orchestrates GSC niche formation, and shed light on how organs utilize the signaling integration to carve out niches.
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