Uygur Aysu, Young John, Huycke Tyler R, Koska Mervenaz, Briscoe James, Tabin Clifford J
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, UK.
Dev Cell. 2016 Apr 18;37(2):127-35. doi: 10.1016/j.devcel.2016.03.024.
Anatomical proportions are robustly maintained in individuals that vary enormously in size, both within a species and between members of related taxa. However, the mechanisms underlying scaling are still poorly understood. We have examined this phenomenon in the context of the patterning of the ventral neural tube in response to a gradient of the morphogen Sonic hedgehog (SHH) in the chick and zebra finch, two species that differ in size during the time of neural tube patterning. We find that scaling is achieved, at least in part, by altering the sensitivity of the target cells to SHH and appears to be achieved by modulating the ratio of the repressive and activating transcriptional regulators, GLI2 and GLI3. This mechanism contrasts with previous experimental and theoretical analyses of morphogenic scaling that have focused on compensatory changes in the morphogen gradient itself.
在体型差异极大的个体中，解剖学比例能够得到稳健维持，这些个体既包括同一物种内的，也包括相关分类群成员之间的。然而，尺寸缩放背后的机制仍知之甚少。我们在鸡和斑胸草雀神经管模式形成的背景下研究了这一现象，这两个物种在神经管模式形成时期大小不同，它们对形态发生素音猬因子（SHH）梯度做出反应。我们发现，尺寸缩放至少部分是通过改变靶细胞对SHH的敏感性来实现的，而且似乎是通过调节抑制性和激活型转录调节因子GLI2和GLI3的比例来实现的。这种机制与之前关于形态发生缩放的实验和理论分析形成对比，之前的分析主要集中在形态发生素梯度本身的补偿性变化上。
