Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling
Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling
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DOI：
10.1002/dvdy.21193
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发表时间：
2007-06-01
影响因子：
2.5
通讯作者：
Pourquie, Olivier
中科院分区：
文献类型：
--
作者：
Goldbeter, Albert;Gonze, Didier;Pourquie, Olivier
胚胎中沿形态原梯度的阈值的建立还知之甚少。通过数学建模，我们证明了相互抑制的梯度可以在胚胎空间产生和定位尖锐的形态生成阈值。以脊椎动物的分割为范例，我们证明了维甲酸(RA)和成纤维细胞生长因子(FGF)沿卵裂期前中胚层(PSM)的拮抗梯度可能导致两个稳定的稳态共存。在这里，我们认为这种双稳定性与成纤维细胞生长因子和类风湿因子信号水平的突变有关，这允许连续的PSM细胞队列中的分段基因同步激活，如Mesp2，以响应分段时钟，从而定义未来的分段。RA和成纤维细胞生长因子的相互抑制所产生的双稳态为“时钟和波前”体细胞发生模型中假设的全有或无转换提供了分子机制。鉴于相互拮抗的信号梯度在发育中很常见，这种双稳开关可能代表了胚胎模式的一个重要原理。
The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning.