In　a　feather,　there　are　distinct　morphologies　along　the　proximal-distal　axis.　The　proximal　part　is　a　cylindrical　stalk　(calamus),　whereas　the　distal　part　has　barb　and　barbule　branches.　Here　we　focus　on　what　molecular　signaling　activity　can　modulate　feather　stem　cells　to　generate　these　distinct　morphologies.　We　demonstrate　the　drastic　tissue　remodeling　during　feather　cycling　which　includes　initiation,　growth　and　resting　phases.　In　the　growth　phase,　epithelial　components　undergo　progressive　changes　from　the　collar　growth　zone　to　the　ramogenic　zone,　to　maturing　barb　branches　along　the　proximal-distal　axis.　Mesenchymal　components　also　undergo　progressive　changes　from　the　dermal　papilla,　to　the　collar　mesenchyme,　to　the　pulp　along　the　proximal-distal　axis.　Over-expression　of　Spry4,　a　negative　regulator　of　receptor　tyrosine　kinases,　promotes　barb　branch　formation　at　the　expense　of　the　epidermal　collar.　It　even　induces　barb　branches　from　the　follicle　sheath　(equivalent　to　the　outer　root　sheath　in　hair　follicles).　The　results　are　feathers　with　expanded　feather　vane　regions　and　small　or　missing　proximal　feather　shafts　(the　calamus).　Spry4　also　expands　the　pulp　region　while　reducing　the　size　of　dermal　papillae,　leading　to　a　failure　to　regenerate.　In　contrast,　over-expressing　Fgf10　increases　the　size　of　the　dermal　papillae,　expands　collar　epithelia　and　mesenchyme,　but　also　prevents　feather　branch　formation　and　feather　keratin　differentiation.　These　results　suggest　that　coordinated　Sprouty/FGF　pathway　activity　at　different　stages　is　important　to　modulate　feather　epidermal　stem　cells　to　form　distinct　feather　morphologies　along　the　proximal-distal　feather　axis.　(c)　2012　Elsevier　Inc.　All　rights　reserved.