Goentoro Lea A, Reeves Gregory T, Kowal Craig P, Martinelli Luigi, Schüpbach Trudi, Shvartsman Stanislav Y
Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Dev Cell. 2006 Aug;11(2):263-72. doi: 10.1016/j.devcel.2006.07.004.
Quantitative information about the distribution of morphogens is crucial for understanding their effects on cell-fate determination, yet it is difficult to obtain through direct measurements. We have developed a parameter estimation approach for quantifying the spatial distribution of Gurken, a TGFalpha-like EGFR ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR system shows that the shape of the Gurken gradient is controlled by a single dimensionless parameter, the Thiele modulus, which reflects the relative importance of ligand diffusion and degradation. By combining the model with genetic alterations of EGFR levels, we have estimated the value of the Thiele modulus in the wild-type egg chamber. This provides a direct characterization of the shape of the Gurken gradient and demonstrates how parameter estimation techniques can be used to quantify morphogen gradients in development.
关于形态发生素分布的定量信息对于理解其对细胞命运决定的影响至关重要，但通过直接测量很难获得。我们开发了一种参数估计方法，用于量化果蝇卵子发生过程中作为形态发生素的类转化生长因子α（TGFalpha）表皮生长因子受体（EGFR）配体Gurken的空间分布。对Gurken/EGFR系统的建模表明，Gurken梯度的形状由一个无量纲参数——蒂勒模数控制，该参数反映了配体扩散和降解的相对重要性。通过将该模型与EGFR水平的基因改变相结合，我们估计了野生型卵室中蒂勒模数的值。这直接表征了Gurken梯度的形状，并展示了如何使用参数估计技术来量化发育过程中的形态发生素梯度。
