Fibroblast growth factor 9 (FGF9) was first identified during a screen for factors acting on cells of the central nervous system (CNS). Research over the subsequent two decades has revealed this protein to be a critically important and elegantly regulated growth factor. A hallmark control feature is reciprocal compartmentalization, particularly during development, with epithelium as a dominant source and mesenchyme a prime target. This mesenchyme selectivity is accomplished by the high affinity of FGF9 to the IIIc isoforms of FGFR1, 2, and 3. FGF9 is expressed widely in the embryo, including the developing heart and lungs, and more selectively in the adult, including the CNS and kidneys. Global Fgf9-null mice die shortly after birth due to respiratory failure from hypoplastic lungs. As well, their hearts are dilated and poorly vascularized, the skeleton is small, the intestine is shortened, and male-to-female sex reversal can be found. Conditional Fgf9-null mice have revealed CNS phenotypes, including ataxia and epilepsy. In humans, FGF9 variants have been found to underlie multiple synostoses syndrome 3, a syndrome characterized by multiple joint fusions. Aberrant FGF9 signaling has also been implicated in differences of sex development and cancer, whereas vascular stabilizing effects of FGF9 could benefit chronic diseases. This primer reviews the attributes of this vital growth factor.

成纤维细胞生长因子 9 (FGF9) 首次在筛选作用于中枢神经系统 (CNS) 细胞的因子时被鉴定出来。随后二十年的研究表明，这种蛋白质是一种极其重要且调控良好的生长因子。一个标志性的控制特征是相互区室化，特别是在发育过程中，上皮细胞是主要来源，间充质是主要目标。这种间充质选择性是通过 FGF9 与 FGFR1、2 和 3 的 IIIc 亚型的高亲和力来实现的。FGF9 在胚胎中广泛表达，包括发育中的心脏和肺，并且在成人中更有选择性地表达，包括中枢神经系统和肾脏。Global Fgf9缺失小鼠在出生后不久就会因肺部发育不良导致的呼吸衰竭而死亡。此外，它们的心脏扩张且血管化不良，骨骼较小，肠道较短，并且可以发现男性对女性的性别逆转。条件性Fgf9缺失小鼠已显示出 CNS 表型，包括共济失调和癫痫。在人类中，已发现 FGF9 变体是多发性骨性骨关节炎综合征 3 的基础，该综合征以多关节融合为特征。异常的 FGF9 信号传导也与性别发育和癌症的差异有关，而 FGF9 的血管稳定作用可能有益于慢性疾病。本入门介绍了这种重要生长因子的属性。