Pickles J O
Vision, Touch and Hearing Research Centre, Department of Physiology and Pharmacology, University of Queensland, 4072, Brisbane, Qld., Australia.
Hear Res. 2001 May;155(1-2):54-62. doi: 10.1016/s0378-5955(01)00247-7.
Four different fibroblast growth factor receptors (FGFR) are known, three of which have splice variants (known as the b and c variants) in the FGF-binding domain, to give different patterns of sensitivity to the different FGFs. The expression of the b and c variants of the FGF receptors, together with the expression of the ligands FGF1, FGF2, FGF3, FGF7, FGF8b and FGF8c, was determined by quantitative reverse transcription-polymerase chain reaction in developing whole mouse inner ears, and in dissected components of the postnatal mouse inner ear. At embryonic age (E)10.5 days, when the otocyst is a simple closed sac, the receptor most heavily expressed was FGFR2b, relative to the postnatal day 0 level. Over the period E10.5-E12.5, during which the structures of the inner ear start to form, the expression of the different FGF receptors increased 10(2)-10(4) fold per unit of tissue, and there was a gradual switch towards expression of the 'c' splice variants of FGFR2 and FGFR3 rather than the 'b' variants. At E10.5, the ligands most heavily expressed, relative to the postnatal day 0 level, were FGF3, FGF8b and FGF8c. In the postnatal inner ear, the patterns of expression of receptors and ligands tended to be correlated, such that receptor variants were expressed in the same regions as the ligands that are known to activate them effectively. The neural/sensory region expressed high levels of FGFR3c, and high levels of the ligand FGF8b. The same area also expressed high levels of FGFR1b and FGFR2b, and high levels of FGF3. The lateral wall of the cochlea (including the stria vascularis and the spiral ligament) expressed high levels of FGFR1c and FGF2. It is suggested that the different FGF receptors and ligands are expressed in a spatially coordinated pattern, to selectively program cochlear development.
已知有四种不同的成纤维细胞生长因子受体(FGFR),其中三种在FGF结合域具有剪接变体(称为b和c变体),从而对不同的FGF产生不同的敏感性模式。通过定量逆转录-聚合酶链反应,测定了发育中的整个小鼠内耳以及出生后小鼠内耳解剖结构中FGF受体b和c变体的表达,以及配体FGF1、FGF2、FGF3、FGF7、FGF8b和FGF8c的表达。在胚胎期(E)10.5天,当耳囊是一个简单的封闭囊时,相对于出生后第0天的水平,表达量最高的受体是FGFR2b。在E10.5 - E12.5期间,内耳结构开始形成,不同FGF受体的表达每单位组织增加了10(2)- 10(4)倍,并且逐渐转向FGFR2和FGFR3的“c”剪接变体而非“b”变体的表达。在E10.5时,相对于出生后第0天的水平,表达量最高的配体是FGF3、FGF8b和FGF8c。在出生后的内耳中,受体和配体的表达模式倾向于相关,使得受体变体在已知能有效激活它们的配体所在的相同区域表达。神经/感觉区域表达高水平的FGFR3c和高水平的配体FGF8b。同一区域还表达高水平的FGFR1b和FGFR2b以及高水平的FGF3。耳蜗的侧壁(包括血管纹和螺旋韧带)表达高水平的FGFR1c和FGF2。有人提出,不同的FGF受体和配体以空间协调的模式表达,以选择性地规划耳蜗的发育。