Differential Cellular Responses to Hedgehog Signalling in Vertebrates-What is the Role of Competence?
Differential Cellular Responses to Hedgehog Signalling in Vertebrates-What is the Role of Competence?
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DOI：
10.3390/jdb4040036
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发表时间：
2016-12-10
影响因子：
2.7
通讯作者：
Logan M
中科院分区：
文献类型：
--
作者：
Kiecker C;Graham A;Logan M
令人惊讶的是，少量的信号传导途径产生了大量的细胞反应，从获得多种细胞命运到增殖、分化、形态发生和细胞死亡。这些不同的反应可能是由于信号因子的剂量依赖性活动，或细胞对给定信号的反应的内在差异-称为差异细胞能力的现象。在这篇综述中，我们专注于刺猬（HH）的信号，是在胚胎和成年生物体的粘附性采用的信号通路的能力的时间和空间差异。我们讨论了上游信号和机制，可能建立不同的能力，在不同的组织范围内的HH。我们认为，不断变化的HH信号能力提供了一个四维框架的信号的解释是必不可少的功能解剖学的出现。许多疾病，包括几种类型的癌症，都是由HH通路的功能障碍引起的。更好地了解是什么提供了这种信号的差异能力，可能会揭示HH相关的疾病机制，并为我们提供更具体的工具来操纵HH信号在临床上。
A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic.