Integrin-associated protein (IAP)是一個與記憶形成相關的細胞附著因子，越來越多的證據顯示IAP 調控了大腦與海馬迴神經培養細胞的分化。Nuclear respiratory factor-1 (NRF-1)是調控IAP 啟動子的重要轉錄因子，其同源蛋白在海膽、果蠅、與斑馬魚等
物種參與神經發育的調控。我們先前的研究證實了NRF-1 可藉由調控IAP 基因表現而促進神經突生長，然而至今IAP 與NRF-1 在哺乳動物的腦發育所扮演的角色尚未
清楚。原位雜合法結果顯示在ICR 小鼠發育過程中, IAP mRNA 廣泛地表現在全腦，尤其在分化中的大腦、海馬迴、丘腦、與小腦。在小腦的發育過程中，IAP mRNA 及蛋白質的表現明顯地隨著小腦顆粒前驅細胞由外顆粒層遷移至內顆粒層而有所變化。免疫組織法分析了IAP 蛋白質在發育中小腦的分布，IAP 表現在分子層、內顆粒層與TAG-1 所辨認的外顆粒層內層。高度表現的IAP 被發現在分子層，且GFAP 未與IAP 同處表現排除了IAP 表現在Bergma glial cells 的radial fibers。而IAP mRNA 在內顆粒層及蛋白質在分子層和內顆粒層的表現也隨著小腦發育而增加，並在成熟的小腦中維持高度的表現。Electrophoretic mobility shift analysis 顯示NRF-1 在含有IAP 啟動子之DNA 結合能力也與發育中小腦的IAP mRNA 與蛋白質表現一致。另外在小腦神經培養細胞中，降低IAP 的表現或競爭掉NRF-1 的功能皆明顯減少神經突的數目與長度。這些結果顯示IAP 與其調控因子NRF-1 參與了腦的發育，尤其在發育中的小腦對小腦顆粒前驅細胞扮演了遷移與分化的角色。

Integirn-associated protein (IAP) is a cell adhesion molecule related to the memory formation. Increasing evidence shows that IAP regulates neuronal differentiation in primary cortical and hippocampal cultured neurons. Nuclear respiratory factor-1 (NRF-1) is a critical transcription factor regulating IAP promoter activity. The homologues of NRF-1 in sea urchin, drosophila, and zebra fish involve in neuronal development. Our previous studies have found that NRF-1 promotes neurite outgrowth in human neuroblastoma cells, which is mediated by the expression of the IAP gene. However, the
roles of NRF-1 and IAP in mammalian brain development are unclear. Using in situ hybridization we found that IAP mRNA was widely expressed in differentiating cortex, hippocampus, thalamus, and cerebellum in ICR mice during development. In developing
cerebellum, the expression of IAP mRNA and protein were accompanied with the
migration of granular cell precursors (GCPs) from external granular layer (EGL) to internal
granular layer (IGL) at postnatal stages. Immunohistochmistry analysis showed that the
distribution of IAP protein in developing cerebellum was expressed in molecular layer (ML), IGL, and the inner layer of EGL. Colocalization of IAP with TAG-1 suggested that
IAP is expressed in postmitotic GCPs. Expression of IAP mRNA in IGL or protein in ML and IGL were gradually increased during cerebellar development and maintained high level in mature cerebellum. Electrophoretic mobility shift analysis showed the DNA binding activity of NRF-1 on the IAP promoter was highly correlated with IAP mRNA and protein expression during the development of cerebellum. Additionally, down-regulation of IAP and competition of NRF-1 function reduced the neurite number and length. These results suggest that IAP and its transcription factor NRF-1 involves in brain development, especially in the migration and differentiation of GCPs in the development of cerebellum.

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