England will field a new-look centre partnership against Italy on Sunday after dropping Jonathan Joseph for the Six Nations clash at Twickenham.
Joseph is omitted from the 24-man squad retained to continue preparations for the next phase of the Grand Slam defence, denying him even a bench role against Conor O'Shea's Azzurri.
It is the second time the Bath centre has been dropped by Eddie Jones, after making way for Elliot Daly in last autumn's victory over South Africa, and it is his rival from Wasps who could also usurp him at outside centre on this occasion.
Owen Farrell, who is set to win his 50th cap, is in contention at fly-half inside a midfield partnership that may see Ben Te'o make his first start alongside Daly.
Te'o made a telling impact when coming off the bench against France and Wales, while Daly has been among England's best performing backs since breaking into the starting XV last autumn.
Anthony Watson is poised to appear in an England match-day squad for the first time since the June tour to Australia after recovering from the hamstring injury he suffered last month.
Along with Daly, Watson is seen as a possible long-term replacement for Mike Brown at full-back.
Brown is present among the 24 and will start against Italy, with Watson, Jonny May and Jack Nowell appearing to be in contention for the wing spots.
England may give James Haskell his first start since the clean sweep of the Wallabies after declaring the openside is fit enough to step up from the 'finisher' role he has performed so far in the Six Nations.
J Clifford (Harlequins), D Cole (Leicester Tigers), J George (Saracens), D Hartley (Northampton Saints), J Haskell (Wasps), N Hughes (Wasps), M Itoje (Saracens), J Launchbury (Wasps), Courtney Lawes (Northampton Saints), Joe Marler (Harlequins), Kyle Sinckler (Harlequins), Mako Vunipola (Saracens), Tom Wood (Northampton Saints).
M Brown (Harlequins), D Care (Harlequins), E Daly (Wasps), O Farrell (Saracens), G Ford (Bath Rugby), J May (Gloucester Rugby), J Nowell (Exeter Chiefs), H Slade (Exeter Chiefs), B Te'o (Worcester Warriors), A Watson (Bath Rugby), B Youngs (Leicester Tigers).