EDA基因及其信号通路在动物皮肤毛囊发育中作用研究进展

Research Progress on EDA Gene and its Role in the Development of Animal Hair Follicle

EDA基因的突变会引起多种外胚层附属物的减少或是缺乏,像头发、牙齿、汗腺、皮脂腺和乳腺等外胚层附属物的生长发育,都需要EDA的参与。EDA信号通路在多种类型毛囊的发生、毛干的形成和皮脂腺的形态发生中发挥作用,它可控制胚胎上皮细胞的命运,调控毛囊细胞的分化过程。作者简述了EDA基因及其信号通路与动物毛囊发育的关系,介绍了EDA基因的功能和蛋白分子结构,以及它主要的两种转录体EDA1和EDA2的功能与作用机制,EDA1-EDAR系统在皮肤衍生结构的发育中发挥主要作用,EDA1和EDAR的突变均会导致HED。阐述了EDA基因信号通路调控毛囊组织生长发育机理以及与多个信号通路的关联,EDA信号可控制毛囊生长期到退行期的转换,对毛囊循环周期中退行期毛囊角质细胞的细胞凋亡起调控作用。EDA-EDAR系统是对皮肤附属器官发育有重要作用的Wnt信号通路的一个重要的效应器,其紧接着出现在Wnt诱导信号的下游。它依靠下游的NF-κB通路的活动来调控靶基因,通过刺激NF-κB调整Wnt、SHH、FGF、和TGF-β信号通路的效应器和抑制因子的转录来发挥作用,调控上皮细胞和间充质细胞还包括组织内的相互作用。结论认为EDA信号通路参与毛囊细胞的发育与分化调控,对动物毛囊生长发育起重要影响作用。

Mutations of the ectodysplasin-A （EDA） gene cause reduction or absence of many ecto- dermal appendages, such as hair, teeth, sweat glands, sebaceous glands and mammary glands, re- quires the action of EDA. EDA signal pathway affects the initiation of several hair follicle （HF） types, hair shaft formation, as well as sebaceous gland morphology, it is involved in the control of cell fate decision in embryonic epidermis, as well as in the regulation of cell differentiation pro- grams in the HF. This paper summarized the relationship between EDA signal pathway and ani- mal HF development. The main content was as follows.. Firstly, the functions of EDA gene and structure of EDA protein,its two main functional splice variants EDA1 and EDA2 ~s functions and mechanism of action,EDA1-EDAR system plays a predominant role in the development of skin- derived structures,EDA1 and EDAR＇s mutations all can cause hypohidrotic ectodermal dysplasia （HED） ;Secondly, the regulation mechanisms of the EDA and its pathway to the HF develop- ment,and also the relationship between EDA and other pathways, studies suggested the involve- ment of EDA signal in control of anagen-catagen transition,it is also involved in hair cycle control and regulates apoptosis in HF keratinocytes during catagen. The EDA-EDAR system is an impor- tant effector of canonical Wnt signal in developing skin appendages,it would then occur directly downstream of the induction signal. The EDA signal pathway relies on downstream NF-kB path- way activation to regulate target genes,it functions by stimulating NF-kB-mediated transcription of effectors or inhibitors of the Wnt,sonic hedgehog （SHH）,fibroblast growth factor （FGF） and transforming growth factor beta （TGF-β） pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. From above, we conclude that EDA and its signal pathway take part in the regulation of HF cell development and differentiation, they play impor- tant role in animal follicle growth and development.