人類第九纖維母細胞生長因子(FGF9)是第九個被發現的纖維母細胞生長因子家族成員，FGF9蛋白具有促進多種神經細胞、腫瘤細胞株生長的能力。在演化上，FGF9的氨基酸序列從線蟲到人類都具有高度的保留性，這顯示出FGF9是一個具有重要功能的基因。在老鼠胚胎發育的多種組織中皆可偵測到有fgf9核糖核酸的表現，並且高度表現在成鼠的大腦與腎臟，這表示FGF9的基因表現受到了嚴密且複雜的機制所調控。在動物模式中，將fgf9專一性大量表現於老鼠的眼球、水晶體會導致老鼠脈絡膜發育異常及白內障；若將之表現在骨骼中，則導致骨骼發育障礙，Fgf9的基因剔除鼠則表現出性別倒置、肺臟發育不全等性狀，並於出生後死亡。動物研究的結果顯示，FGF9在人類胚胎發育、器官形成、性別發展和維持生命機能上極可能扮演重要角色，然而目前對於人類FGF9基因的表現、調控和細胞功能的研究十分有限。利用DNA序列分析，我們發現在FGF9基因的序列上發現多處微衛星序列(microsatellite)，另外也在FGF9基因啟動子區上發現許多轉錄因子(transcription factor; TF)的結合序列。由於近來許多研究顯示位在非轉譯區的微衛星序列對於基因的調控扮演非常重要的角色。因此，這個實驗的主要目的在於釐清這些位於FGF9基因區的微衛星序列及轉錄因子結合序列對於FGF9的表現是否有影響。我們將位於FGF9基因轉譯起始點上游2.2kb的核酸片段複製並利用報導基因系統加以研究。實驗結果顯示位於三端未轉譯區的微衛星序列具有調節FGF9基因表現的能力，且此調節力似乎是具有組織專一性的。另外由連續性刪除序列實驗發現FGF9基因的-799~-712區間與五端未轉譯區對於其調節FGF9基因表現的能力扮演相當重要的角色。

Fibroblast growth factor 9 (FGF9) is the ninth member of FGF family, and functions as a secreted mitogen for several kinds of cells. Sequences of FGF9 gene are highly conserved from C. elegans to human, indicating that functions of FGF9 are very important. Mouse Fgf9 mRNA are detected in several tissues during embryogenesis, and highly expressed in adult kidney and brain. Ectopic expression of FGF9 in mice reveals that FGF9 is the core regulator for bone and eye development. Moreover, Fgf9 knock-out mice exhibit lung hypoplasia, early postnatal death, and male to female sex reversal. These studies suggested that FGF9 is a multifunctional protein, which plays important roles in embryonic development, organ development, sexual development and physiologic maintenances. However, limited studies about FGF9 gene regulation in human have been reported. By sequence analysis, several microsatellite (MS) motifs as well as many transcription factors (TF) binding sites were found in the FGF9 gene. Currently more and more studies have demonstrated that MS motifs in noncoding region could play important roles in gene regulation. The aims of this study are to illustrate potential effects of these MS motifs and TF binding sites in regulating FGF9 gene expression. The 3’UTR MS motif and a 2.2 kb DNA fragment upstream from the FGF9 transcriptional starting site have been cloned and analyzed by using reporter gene system. Our data showed that the MS motif of FGF9 3’UTR can modulate FGF9 gene expression in a tissue-specific manner. In addition, from serial deletion analysis of FGF9 5’ promoter region showed that the -799~-712 interval and 5’UTR regions of the FGF9 gene are important for gene expression.

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