The Edar subfamily in feather placode formation

Abstract

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-κB, 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.