不論是發育中或是成熟的腦部， self-renewal對於維持神經幹細胞 (neural stem cell, 神經幹細胞) 的數目相當重要。在神經系統發育的過程中，需要精確地維持神經幹細胞的self-renewal與神經元新生之間的平衡，才能確使發育後的神經系統具有正確的細胞類型及數目。目前對於神經幹細胞self-renewal的調控機制的瞭解仍相當有限。過去的研究發現Krüppel-like zinc finger 家族中的一員，zbtb16又稱為早幼粒白血病鋅指蛋白 (Promyelocytic leukemia zinc finger, PLZF)，表現在早期的中樞神經系統，並隨著神經系統的發育在特定的區域受到調控。此外，PLZF在血球前趨細胞 (Hematopoietic stem cell) 及精原幹細胞 (spermatogonial stem cell, SCC) 中也都有表現，且被認為參與在胚胎發育、造血作用 (hematopoiesis) 及造精作用 (spermatohenesis) 中。在本論文中，我們發現PLZF在P19分化為神經細胞的過程中會短暫地表現。利用RNA 干擾技術 (RNA interference) 抑制PLZF表現，結果也顯示會降低神經幹細胞標記蛋白Nestin及Pax6的表現，同時在分化過程中形成的embryonal body 也較小 。上述實驗結果顯示PLZF在P19細胞進行神經細胞分化過程中對具有類似神經幹細胞特性的細胞有調控作用。更重要的是我們進一步發現，在PLZF基因突變造成功能缺失的小鼠中，其大腦半球明顯地小於野生型 (wild type) 及異型合子 (hetrozygote) 小鼠。顯示PLZF的確可能參與調控神經幹細胞的self-renewal。

Self-renewal is important for the maintenance of the neural stem cell pool in developing and adult brains. During nervous system development, the proper balance between stem cell self-renewal and neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms that control neural stem cell self-renewal remain poorly understood. Zbtb16 is also called Promyelocytic leukemia zinc finger (PLZF), a Krüppel-like zinc finger gene, is expressed in spatially restricted and temporally dynamic patterns in the central nervous system. Moreover, PLZF is found to be required for maintenace of the stem cell of various lineages, such as hematopoietic stem cells and spermatogonial stem cells and implicated in embryonal development, hematopoiesis, and spermatogenesis [1-5]. In our study, PLZF shows a temporal expression pattern during neural differentiation of P19 cells. Inhibition of PLZF induction by RNA interference leads to attenuated expression of neural stem cell markers, Nestin and Pax6, and generated smaller embryoid bodies, suggesting that expression of PLZF regulates the neural stem cell-like properties. More importantly, we found that the cortical hemisphere of lu mice, a PLZF-mutant mice, is significantly smaller than that of WT and heterozygous littermates. These results indicate that PLZF may regulate neural stem cell self-renewal and involve in brain development.

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