As an essential feature of development, robustness ensures that embryos attain a consistent phenotype despite genetic and environmental variation. The growing number of examples demonstrating that embryos can mount a compensatory response to germline mutations in key developmental genes has heightened interest in the phenomenon of embryonic robustness. While considerable progress has been made in elucidating genetic compensation in response to germline mutations, the diversity, mechanisms, and limitations of embryonic robustness remain unclear. In this work, we have examined whether Xenopus laevis embryos are able to compensate for perturbations of the Notch signaling pathway induced by RNA injection constructs that either upregulate or inhibit this signaling pathway. Consistent with earlier studies, we found that at neurula stages, hyperactivation of the Notch pathway inhibited neural differentiation while inhibition of Notch signaling increases premature differentiation as assayed by neural beta tubulin expression. However, surprisingly, by hatching stages, embryos begin to compensate for these perturbations, and by swimming tadpole stages most embryos exhibited normal neuronal gene expression. Using cell proliferation and TUNEL assays, we show that the compensatory response is, in part, mediated by modulating levels of cell proliferation and apoptosis. This work provides an additional model for addressing the mechanisms of embryonic robustness and of genetic compensation.

作为发育的一个基本特征，稳健性可确保胚胎在遗传和环境变化的情况下获得一致的表型。越来越多的例子表明，胚胎可以对关键发育基因的种系突变产生补偿性反应，这引起了人们对胚胎稳健性现象的兴趣。虽然在阐明针对种系突变的遗传补偿方面已经取得了相当大的进展，但胚胎稳健性的多样性、机制和局限性仍不清楚。在这项工作中，我们检查了非洲爪蟾胚胎是否能够补偿由 RNA 注射构建体诱导的 Notch 信号通路的扰动，这些构建体上调或抑制该信号通路。与早期的研究一致，我们发现在神经胚阶段，Notch 通路的过度激活抑制神经分化，而通过神经 β 微管蛋白表达检测，Notch 信号传导的抑制会增加过早分化。然而，令人惊讶的是，到了孵化阶段，胚胎开始补偿这些扰动，并且到了游泳蝌蚪阶段，大多数胚胎表现出正常的神经元基因表达。使用细胞增殖和 TUNEL 测定，我们表明补偿反应部分是通过调节细胞增殖和凋亡水平介导的。这项工作为解决胚胎稳健性和遗传补偿机制提供了另一个模型。