Drew Caroline F, Lin Chih Min, Jiang Ting Xin, Blunt Geoff, Mou Chunyan, Chuong Cheng Ming, Headon Denis J
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Dev Biol. 2007 May 1;305(1):232-45. doi: 10.1016/j.ydbio.2007.02.011. Epub 2007 Feb 16.
A subgroup of the TNF receptor family, composed of Edar, Troy and Xedar, are implicated in the development of ectodermal appendages, such as hair follicles, teeth and sweat glands. We have isolated chicken orthologues of these three receptors and analysed their roles in early feather development. Conservation of protein sequences between mammalian and avian proteins is variable, with avian Edar showing the greatest degree of sequence identity. cXedar differs from its mammalian orthologue in that it contains an intracellular death domain. All three receptors are expressed during early feather morphogenesis and dominant negative forms of each receptor impair the epithelial contribution to feather bud morphogenesis, while the dermal contribution appears unaffected. Hyperactivation of each receptor leads to more widespread assumption of placode fate, though in different regions of the skin. Receptor signaling converges on NF-kappaB, and inhibiting this transcription factor alters feather bud number and size in a stage-specific manner. Our findings illustrate the roles of these three receptors during avian skin morphogenesis and also suggest that activators of feather placode fate undergo mutual regulation to reach a decision on skin appendage location and size.
肿瘤坏死因子受体家族的一个亚组，由Edar、Troy和Xedar组成，与外胚层附属器（如毛囊、牙齿和汗腺）的发育有关。我们已经分离出这三种受体的鸡直系同源物，并分析了它们在早期羽毛发育中的作用。哺乳动物和鸟类蛋白质之间的蛋白质序列保守性各不相同，其中鸟类Edar的序列同一性程度最高。cXedar与其哺乳动物直系同源物的不同之处在于它含有一个细胞内死亡结构域。所有三种受体在早期羽毛形态发生过程中均有表达，每种受体的显性负性形式都会损害上皮细胞对羽毛芽形态发生的贡献，而真皮细胞的贡献似乎未受影响。每种受体的过度激活会导致在皮肤的不同区域更广泛地出现基板命运。受体信号传导汇聚于核因子κB，抑制该转录因子会以阶段特异性方式改变羽毛芽的数量和大小。我们的研究结果阐明了这三种受体在鸟类皮肤形态发生过程中的作用，也表明羽毛基板命运的激活因子会相互调节，以决定皮肤附属器的位置和大小。
