Department of Cell Biology and Molecular Genetics, University of Maryland, Maryland, United States.
Elife. 2018 Oct 17;7:e38137. doi: 10.7554/eLife.38137.
Gradients of signaling proteins are essential for inducing tissue morphogenesis. However, mechanisms of gradient formation remain controversial. Here we characterized the distribution of fluorescently-tagged signaling proteins, FGF and FGFR, expressed at physiological levels from the genomic knock-in alleles in . FGF produced in the larval wing imaginal-disc moves to the air-sac-primordium (ASP) through FGFR-containing cytonemes that extend from the ASP to contact the wing-disc source. The number of FGF-receiving cytonemes extended by ASP cells decreases gradually with increasing distance from the source, generating a recipient-specific FGF gradient. Acting as a morphogen in the ASP, FGF activates concentration-dependent gene expression, inducing at higher and at lower levels. The transcription-factors Pointed-P1 and Cut antagonize each other and differentially regulate formation of FGFR-containing cytonemes, creating regions with higher-to-lower numbers of FGF-receiving cytonemes. These results reveal a robust mechanism where morphogens self-generate precise tissue-specific gradient contours through feedback regulation of cytoneme-mediated dispersion.
信号蛋白梯度对于诱导组织形态发生至关重要。然而，梯度形成的机制仍存在争议。在这里，我们描述了在生理水平上从基因组敲入等位基因中表达的荧光标记的信号蛋白 FGF 和 FGFR 的分布。幼虫翅膀 imaginal-disc 中产生的 FGF 通过含有 FGFR 的纤毛运动到气囊原基 (ASP)，纤毛从 ASP 延伸以接触 wing-disc 来源。随着与源的距离增加，ASP 细胞延伸的 FGF 受体纤毛的数量逐渐减少，从而产生具有受体特异性的 FGF 梯度。作为 ASP 中的形态发生素，FGF 激活浓度依赖性基因表达，在较高水平诱导 ，在较低水平诱导 。转录因子 Pointed-P1 和 Cut 相互拮抗，并且差异调节含有 FGFR 的纤毛的形成，从而形成具有较高到较低数量的 FGF 受体纤毛的区域。这些结果揭示了一种强大的机制，其中形态发生素通过纤毛介导的扩散的反馈调节来自我产生精确的组织特异性梯度轮廓。
