Wnt signals provide a timing mechanism for the FGF-retinoid differentiation switch during vertebrate body axis extension
Wnt signals provide a timing mechanism for the FGF-retinoid differentiation switch during vertebrate body axis extension
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DOI：
10.1242/dev.000216
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发表时间：
2007-06-01
期刊：
影响因子：
4.6
通讯作者：
Storey, Kate G.
中科院分区：
文献类型：
--
作者：
Olivera-Martinez, Isabel;Storey, Kate G.
脊椎动物体轴的分化起始是由从成纤维细胞生长因子（FGF）到类维生素A信号传导的保守转换控制的，这在延伸的肢体中也很明显，并且在许多癌细胞系中是异常的。 FGF 通过抑制类视黄醇合成来保护尾端干区细胞免于早熟分化，而后期产生的视黄酸 (RA) 会减弱 FGF 信号传导并促进分化。因此，RA 产生的时机对于干区细胞的保存和身体轴的持续延伸至关重要。在这里，我们表明，经典的 Wnt 信号传导介导新生成的鸡体轴中从 FGF 到类视黄醇信号传导的转变。 FGF 促进 Wnt8c 表达，随着 FGF 信号传导减弱，Wnt8c 持续存在于神经上皮中。然后 Wnt 信号在此发挥作用，抑制神经元分化。此外，虽然 FGF 对神经元分化的抑制涉及 RA 反应基因、视黄酸受体 β (RAR β) 的抑制，但 Wnt 信号是神经元产生的较弱抑制因子，不会干扰 RA 信号转导。引人注目的是，随着延伸轴中 FGF 信号的减弱，Wnt 信号现在会在邻近的前体中胚层中引发 RA 合成。这项研究确定了从 FGF 到类视黄醇信号传导的定向信号传递，并证明当细胞离开干区时，Wnt 信号可以允许和促进 RA 活性，从而提供一种控制 FGF-RA 分化转换时间的机制。
Differentiation onset in the vertebrate body axis is controlled by a conserved switch from fibroblast growth factor (FGF) to retinoid signalling, which is also apparent in the extending limb and aberrant in many cancer cell lines. FGF protects tail-end stem zone cells from precocious differentiation by inhibiting retinoid synthesis, whereas later-produced retinoic acid ( RA) attenuates FGF signalling and drives differentiation. The timing of RA production is therefore crucial for the preservation of stem zone cells and the continued extension of the body axis. Here we show that canonical Wnt signalling mediates the transition from FGF to retinoid signalling in the newly generated chick body axis. FGF promotes Wnt8c expression, which persists in the neuroepithelium as FGF signalling declines. Wnt signals then act here to repress neuronal differentiation. Furthermore, although FGF inhibition of neuronal differentiation involves repression of the RA-responsive gene, retinoic acid receptor beta (RAR beta), Wnt signals are weaker repressors of neuron production and do not interfere with RA signal transduction. Strikingly, as FGF signals decline in the extending axis, Wnt signals now elicit RA synthesis in neighbouring presomitic mesoderm. This study identifies a directional signalling relay that leads from FGF to retinoid signalling and demonstrates that Wnt signals serve, as cells leave the stem zone, to permit and promote RA activity, providing a mechanism to control the timing of the FGF-RA differentiation switch.