Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
J Neurosci. 2010 Jan 13;30(2):685-93. doi: 10.1523/JNEUROSCI.4165-09.2010.
Axons are guided to their targets by molecular cues expressed in their environment. How is the presence of these cues regulated? Although some evidence indicates that morphogens establish guidance cue expression as part of their role in patterning tissues, an important question is whether morphogens are then required to maintain guidance signals. We found that fibroblast growth factor (FGF) signaling sustains the expression of two guidance cues, semaphorin3A (xsema3A) and slit1 (xslit1), throughout the period of Xenopus optic tract development. With FGF receptor inhibition, xsema3A and xslit1 levels were rapidly diminished, and retinal ganglion cell axons arrested in the mid-diencephalon, before reaching their target. Importantly, direct downregulation of XSema3A and XSlit1 mostly phenocopied this axon guidance defect. Thus, FGFs promote continued presence of specific guidance cues critical for normal optic tract development, suggesting a second later role for morphogens, independent of tissue patterning, in maintaining select cues by acting to regulate their transcription.
轴突通过其环境中表达的分子线索被引导到其靶标。这些线索的存在是如何调节的？尽管有一些证据表明形态发生素在组织模式形成过程中建立了导向线索表达，是其作用的一部分，但一个重要的问题是形态发生素是否随后需要维持导向信号。我们发现，在整个非洲爪蟾视神经束发育过程中，纤维母细胞生长因子 (FGF) 信号持续维持两种导向线索，即神经丝氨酸 3A（xsema3A）和裂隙 1（xslit1）的表达。FGF 受体抑制后，xsema3A 和 xslit1 的水平迅速下降，视网膜神经节细胞轴突在到达靶标之前在中脑间停止。重要的是，XSema3A 和 XSlit1 的直接下调主要模拟了这种轴突导向缺陷。因此，FGF 促进了对正常视神经束发育至关重要的特定导向线索的持续存在，这表明形态发生素在维持选择线索方面具有第二个后期作用，独立于组织模式形成，通过调节其转录来发挥作用。
