Shaping BMP morphogen gradients through enzyme-substrate interactions.
Shaping BMP morphogen gradients through enzyme-substrate interactions.
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DOI：
10.1016/j.devcel.2011.06.025
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发表时间：
2011-08-16
影响因子：
11.8
通讯作者：
Serpe, Mihaela
中科院分区：
文献类型：
--
作者：
Peluso, Carolyn E.;Umulis, David;Kim, Young-Jun;O'Connor, Michael B.;Serpe, Mihaela
骨形态发生蛋白（BMPs）调节整个动物王国的背/腹（D/V）模式;然而，某些途径组分的生化特性可能会因物种特异性发育要求而异。例如，Tolloid（Tld）样金属蛋白酶组成性地切割脊椎动物BMP结合蛋白，称为Chordins，而果蝇Chordin直系同源物，短原肠胚形成（Sog），仅在与BMP结合时才被有效切割。我们确定了负责使其裂解依赖于BMP结合的Sog特征。独立于BMP处理的“类腱索”变体将果蝇胚胎中发现的陡峭BMP梯度改变为较浅的轮廓，类似于在一些脊椎动物胚胎中观察到的。这种变化最终影响了细胞命运分配和组织大小，并导致图案化的可变性增加。因此，在进化过程中获得BMP依赖的Sog处理似乎有利于长距离配体扩散和形成一个强大的形态梯度，使早期果蝇图案所需的BMP信号输出。
Bone Morphogenetic Proteins (BMPs) regulate dorsal/ventral (D/V) patterning across the animal kingdom; however, the biochemical properties of certain pathway components can vary according to species-specific developmental requirements. For example, Tolloid (Tld)-like metalloproteases cleave vertebrate BMP-binding proteins called Chordins constitutively, while the Drosophila Chordin ortholog, Short gastrulation (Sog), is only cleaved efficiently when bound to BMPs. We identified Sog characteristics responsible for making its cleavage dependent on BMP binding. “Chordin-like” variants that are processed independently of BMPs, changed the steep BMP gradient found in Drosophila embryos to a shallower profile, analogous to that observed in some vertebrate embryos. This change ultimately affected cell fate allocation and tissue size and resulted in increased variability of patterning. Thus, the acquisition of BMP-dependent Sog processing during evolution appears to facilitate long-range ligand diffusion and formation of a robust morphogen gradient, enabling the bistable BMP signaling outputs required for early Drosophila patterning.
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