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The government and business will herald a "landmark moment" in improving the North West's rail connections on Monday when the bill to extend HS2 to Manchester is laid in Parliament.
Phase 2b of the high-speed line will cut journey times by 55 minutes from London to Manchester, ministers say.
The bill laid on Monday seeks powers to lay new track and build new stations.
Work is under way on phase one of HS2 between London and Birmingham. It is set to open between 2029 and 2033.
The next section will extend the line to Crewe, with the final phase taking HS2 to Manchester - with that part of the line expected to open between 2035 and 2040.
Transport Secretary Grant Shapps said: "We are determined to improve transport connections and level up communities across the country, and this bill marks a landmark moment as we bring HS2 to Manchester and lay the foundations for Northern Powerhouse Rail."
HS2 Ltd, the organisation delivering the railway, said phase 2b would deliver "significant connectivity, reliability and journey time benefits" for passengers travelling between Scotland, the North, the Midlands and the South East.
Among other things, the 52-mile route includes new high-speed stations at Manchester Airport and Manchester Piccadilly.
It will also provide the infrastructure required for Northern Powerhouse Rail - a new high-speed line between Warrington, Manchester and Marsden in Yorkshire
Some 17,500 construction jobs are expected to be created, HS2 limited said.
'Vote of confidence'
"HS2 has an integral role to play in levelling up and rebalancing Britain's economy, and this extension of the network fuels that role by bringing the country's economic centres in the North and Midlands closer together," HS2 Ltd boss Mark Thurston said.
"Construction of the first phase of HS2 is already supporting over 20,000 jobs and spearheading investment and growth in major population centres along the route," he added.
"This bill is a vote of confidence in HS2's ability to help towns and cities in the North realise their economic potential."
In November, the government sparked outrage when it scrapped the planned extension of HS2 from East Midlands Parkway to Leeds.
Instead it promised to deliver similar benefits, faster and more cheaply, through its scaled back Integrated Rail Plan.
However, business leaders in the Midlands and North accused the government of reneging on its investment promises, noting many journey times would now be slower than under the previous proposals.