Shaping a Morphogen Gradient for Positional Precision
Shaping a Morphogen Gradient for Positional Precision
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DOI：
10.1016/j.bpj.2010.04.073
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发表时间：
2010-08-04
影响因子：
3.4
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
He, Feng;Saunders, Timothy E.;Ma, Jun
形态梯度为发育中的组织中的细胞提供位置信息，原则上可以采用任何不均匀的轮廓。据我们所知，形态梯度的轮廓如何影响位置精度还没有得到很好的实验研究。在这里，我们比较了果蝇形态发生蛋白BCD(BCD)在野生型(Wt)胚胎和缺乏相互作用辅助因子的胚胎中提供的位置精度。后一种情况下的BCD梯度与其对应的wt相比，在胚胎中期附近的位置精度降低。驼背(HB)是BCD激活的靶点，其结构域边界在突变胚胎中变得更加可变。通过考虑胚胎到胚胎、内部和测量波动，我们从数学上剖析了导致位置信息误差的相关波动来源。使用这种方法，我们证明了突变胚胎中Hb边界定位的缺陷直接反映了BCD梯度轮廓的改变，向中期胚胎的平坦度增加。此外，我们发现BCD输入信号中的噪声主要受内部波动的影响，但由于时间和空间平均，HB边界的空间精度主要受胚胎到胚胎的变化的影响。我们的结果表明，wt BCD梯度轮廓提供的位置信息是高精度的，是图案精度所必需的。
Morphogen gradients, which provide positional information to cells in a developing tissue, could in principle adopt any nonuniform profile. To our knowledge, how the profile of a morphogen gradient affects positional precision has not been well studied experimentally. Here, we compare the positional precision provided by the Drosophila morphogenetic protein Bicoid (Bcd) in wild-type (wt) embryos with embryos lacking an interacting cofactor. The Bcd gradient in the latter case exhibits decreased positional precision around mid-embryo compared with its wt counterpart. The domain boundary of Hunchback (Hb), a target activated by Bcd, becomes more variable in mutant embryos. By considering embryo-to-embryo, internal, and measurement fluctuations, we dissect mathematically the relevant sources of fluctuations that contribute to the error in positional information. Using this approach, we show that the defect in Hb boundary positioning in mutant embryos is directly reflective of an altered Bcd gradient profile with increasing flatness toward mid-embryo. Furthermore, we find that noise in the Bcd input signal is dominated by internal fluctuations but, due to time and spatial averaging, the spatial precision of the Hb boundary is primarily affected by embryo-to-embryo variations. Our results demonstrate that the positional information provided by the wt Bcd gradient profile is highly precise and necessary for patterning precision.