Morphogen gradients in development: from form to function
Morphogen gradients in development: from form to function
复制标题
DOI：
10.1002/wdev.2
复制
发表时间：
2012-01-01
影响因子：
--
通讯作者：
Christian, Jan L.
中科院分区：
文献类型：
--
作者：
Christian, Jan L.
形态因子是一种以剂量依赖的方式建立梯度分布并引起不同细胞反应的物质。它们的功能是为字段内的单个细胞提供位置信息，这些信息被解释为产生空间模式。形成因子可以由胞内因子组成，通过在细胞质中扩散而形成浓度梯度。更常见的是，形态因子包括分泌的蛋白质，这些蛋白质在细胞场中形成细胞外梯度。实验研究和计算分析为细胞外形态梯度形成的多种策略提供了支持。这些包括细胞外空间的自由扩散，与硫酸肝素蛋白聚糖相互作用的限制性扩散，含脂载体的运输或可溶性结合伙伴的运输。更特殊的运输方式也被假设，如胞吞作用，其中反复的分泌，内吞作用和细胞内运输通过细胞而不是围绕细胞移动形态形成因子，或细胞素，由来自信号接收细胞的丝状延伸组成，假设到达形态形成因子发送细胞。一旦梯度形成，细胞必须区分形态原浓度的微小差异，即使在梯度消失后也要储存这些信息。这通常是通过将配体浓度转化为被内化并继续从内体室发出信号的活化细胞表面受体数量的比例增加来实现的。最终，这导致一个或几个转录因子的激活，这些转录因子将这些信息转导成细胞核内质量不同的基因反应。(C) 2011 Wiley期刊公司
Morphogens are substances that establish a graded distribution and elicit distinct cellular responses in a dose-dependent manner. They function to provide individual cells within a field with positional information, which is interpreted to give rise to spatial patterns. Morphogens can consist of intracellular factors that set up a concentration gradient by diffusion in the cytoplasm. More commonly, morphogens comprise secreted proteins that form an extracellular gradient across a field of cells. Experimental studies and computational analyses have provided support for a number of diverse strategies by which extracellular morphogen gradients are formed. These include free diffusion in the extracellular space, restricted diffusion aided by interactions with heparan sulfate proteoglycans, transport on lipid-containing carriers or transport aided by soluble binding partners. More specialized modes of transport have also been postulated such as transcytosis, in which repeated rounds of secretion, endocytosis, and intracellular trafficking move morphogens through cells rather than around them, or cytonemes, which consist of filopodial extensions from signal-receiving cells that are hypothesized to reach out to morphogen-sending cells. Once the gradient has formed, cells must distinguish small differences in morphogen concentration and store this information even after the gradient has dissipated. This is often achieved by translating ligand concentration into a proportional increase in numbers of activated cell surface receptors that are internalized and continue to signal from endosomal compartments. Ultimately, this leads to activation of one or a few transcription factors that transduce this information into qualitatively distinct gene responses inside the nucleus. (C) 2011 Wiley Periodicals, Inc.