Ipiña Emiliano Perez, Dawson Silvina Ponce
Departamento de Física, FCEN-UBA, and IFIBA, CONICET, Ciudad Universitaria, Pabellón I, (1428) Buenos Aires, Argentina. Laboratoire J. A. Dieudonné Université de Nice Sophia Antipolis, UMR 7351 CNRS, Parc Valrose, F-06108 Nice Cedex 02, France. Author to whom any correspondence should be addressed.
Phys Biol. 2017 Feb 8;14(1):016002. doi: 10.1088/1478-3975/aa56d9.
During early development, the establishment of gradients of transcriptional factors determines the patterning of cell fates. The case of Bicoid (Bcd) in Drosophila melanogaster embryos is well documented and studied. There are still controversies as to whether SDD models in which Bcd is Synthesized at one end, then Diffuses and is Degraded can explain the gradient formation within the timescale observed experimentally. The Bcd gradient is observed in embryos that express a Bicoid-eGFP fusion protein (Bcd-GFP) which cannot differentiate if Bcd is freely diffusing or bound to immobile sites. In this work we analyze an SDID model that includes the Interaction of Bcd with binding sites. We simulate numerically the resulting full reaction-diffusion system in a cylindrical domain using previously determined biophysical parameters and a simplified version of the Bcd source. In this way we obtain solutions that depend on the spatial location approximately as observed experimentally and that reach such dependence at a time that is also compatible with the experimental observations. Analyzing the differences between the free and bound Bcd distributions we observe that the latter spans over a longer lengthscale. We conclude that deriving the lengthscale from the distribution of Bcd-GFP can lead to an overestimation of the gradient lengthscale and of the Hill coefficient that relates the concentrations of Bcd and of the protein, Hunchback, whose production is regulated by Bcd.
在早期发育过程中，转录因子梯度的建立决定了细胞命运的模式。果蝇胚胎中Bicoid（Bcd）的情况已有充分记录和研究。对于Bcd在一端合成、然后扩散并降解的SDD模型是否能在实验观察到的时间尺度内解释梯度形成，仍存在争议。在表达Bicoid-eGFP融合蛋白（Bcd-GFP）的胚胎中观察到了Bcd梯度，而如果Bcd自由扩散或与固定位点结合，该融合蛋白无法区分。在这项工作中，我们分析了一个包括Bcd与结合位点相互作用的SDID模型。我们使用先前确定的生物物理参数和Bcd源的简化版本，在圆柱形区域对由此产生的完整反应扩散系统进行了数值模拟。通过这种方式，我们获得了依赖于空间位置的解，其大致与实验观察结果一致，并且在与实验观察结果也相符的时间达到这种依赖性。分析自由Bcd和结合Bcd分布之间的差异，我们观察到后者跨越的长度尺度更长。我们得出结论，从Bcd-GFP的分布推导长度尺度可能会导致对梯度长度尺度以及将Bcd浓度与蛋白质Hunchback浓度相关联的希尔系数的高估，Hunchback的产生受Bcd调节。
