The ectodysplasin pathway in feather tract development
The ectodysplasin pathway in feather tract development
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DOI：
10.1242/dev.01651
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发表时间：
2005-03-01
期刊：
影响因子：
4.6
通讯作者：
Morgan, BA
中科院分区：
文献类型：
--
作者：
Houghton, L;Lindon, C;Morgan, BA
外胚层发育不良途径，包括配体外胚层发育不良，其受体Edar和一个专门的死亡结构域衔接蛋白Edaradd，在哺乳动物的表皮器官形成中发挥重要作用。编码这些蛋白质的基因突变会导致牙齿、汗腺和毛囊发育不良或缺失。然而，这一途径在指导卵泡形成的调控层次中的相对位置仍不清楚。在这项工作中，鸡直系同源的埃达，埃达和Edaradd克隆利用羽道系统的时间精度，以研究外胚层发育不良途径的作用。我们发现，这些基因在羽毛和毛发发育过程中以相似的模式表达，具有显著差异的是，在小鼠表皮中表达的配体Eda在羽道的真皮中表达。相反的突变小鼠的分析得出的结论，我们发现，本地化的Edar表达的新生基板是一致的或随后的基板分化的其他标志物的本地表达，而不是在道图案的上游事件。此外，BMP和活化的β-连环蛋白的强制表达表明，Edar的局部表达是由这两种途径之间的相互作用决定的。这些结果表明，外胚层发育不良途径的激活可能是允许的激活信号，以克服抑制基板形成的信号，但该途径的功能，在卵泡启动的规格在于下游的其他图案化事件。
The ectodysplasin pathway, comprising the ligand ectodysplasin, its receptor Edar and a dedicated death domain adaptor protein Edaradd, plays an important role in epidermal organ formation in mammals. Mutations in the genes encoding these proteins cause dysplasia or absence of teeth, sweat glands and hair follicles. However, the relative position of this pathway in the regulatory hierarchy directing follicle formation remains unclear. In this work, the chicken orthologs of Eda, Edar and Edaradd were cloned to exploit the temporal precision of the feather tract system in order to study the role of the ectodysplasin pathway. We find that these genes are expressed in a similar pattern during feather and hair development, with the notable difference that the ligand Eda, which is expressed in the epidermis of the mouse, is expressed in the dermis of the feather tract. Contrary to conclusions reached from the analysis of mutant mice, we find that localization of Edar expression to the nascent placode is coincident or subsequent to the local expression of other markers of placodal differentiation, and not an upstream event in tract patterning. Furthermore, forced expression of BMP and activated beta-catenin demonstrate that local expression of Edar is dictated by the interaction between these two pathways. These results suggest that activation of the ectodysplasin pathway may be permissive for activating signals to overcome signals that inhibit placode formation, but the function of this pathway in the specification of follicle initiation lies downstream of other patterning events.