England will enter the Autumn without four of their biggest names including the Vunipola brothers after Eddie Jones prioritised youth in a re-generation of the squad.
With the 2023 World Cup in mind, Mako and Billy Vunipola, Jamie George and George Ford have been overlooked for the 34-man squad picked for next month's Tests against Tonga, Australia and South Africa.
Forwards Billy and Mako Vunipola and George have been left out, despite excelling for Saracens since their initial snub from the extended training squad named a month ago.
Ford's generalship has been a key factor behind Leicester's emergence as runaway Gallagher Premiership leaders after five rounds, but the fly-half, another mainstay of the Jones era, is omitted once more.
Jack Nowell, the Exeter wing with a lengthy injury history, and Wasps scrum-half Dan Robson have also been jettisoned ahead of a campaign that opens against Tonga at Twickenham on November 6.
"We've drawn a line in the sand after the Lions series and we're looking to produce a younger squad to get ready for the World Cup," said Jones, who has confirmed that Owen Farrell will continue as captain.
"It doesn't mean those guys are out of the picture. I have been pleased with the way they've responded at club level.
"I spoke to them this (Monday) morning and they know where they stand, so at the moment we're running with this young but very good squad.
"I don't think it's a new England squad because there are a number of good players remaining from the previous World Cup campaign and they'll continue to be important.
"But what we've done is add some youth and enthusiasm. It's an opportunity for the squad to keep getting better."
Maro Itoje (shoulder), Anthony Watson (knee) and Luke Cowan-Dickie (ankle) were injured during the weekend's Gallagher Premiership action and Jones revealed that they will undergo scans this week.
Leicester hooker Nic Dolly and Northampton full-back Tommy Freeman make their first appearances in a senior England squad, while Gloucester centre Mark Atkinson and Sale scrum-half Raffi Quirke complete an uncapped quartet.
"Freeman's a big, strong, strapping lad. He's got good pace, a good feel for the game. He can play full-back or wing. I've been watching him for a couple of seasons," Jones said.
"Dolly's just come into the Premiership this year. He's an industrious player who has been very impressive for Leicester and we feel like he can make the jump to Test rugby."
Marcus Smith is one of eight who made their debuts in the July victories over the USA and Canada to survive the cull from 45 to 34 players, with the Harlequins fly-half's inclusion coming at Ford's expense.
Excitement is building over Smith as he continues to thrill audiences with his swashbuckling endeavours in the Premiership, in addition to an outing against the Stormers as a late call-up for the Lions, but Jones is wary of adding his voice to the chorus of approval.
"First of all, he's got to get in the side. That's the number one step. He's one of 34 players trying to get in the 23. If he does that, then there's an opportunity for him to add his own flavour and strengths to the team," Jones said.
While Jones is looking to the future in selecting his most eventful squad yet, some developing prospects have been unable to force their way into contention either.
Ollie Lawrence, Louis Lynagh, Joe Marchant, Lewis Ludlow and Beno Obano have been removed after winning places in the initial training group announced last month.