Mr Isherwood urged AMs of all parties to recognise the distinct advantages Wales enjoys through its union with England, Scotland and Northern Ireland as part of a strong United Kingdom.
Referring to the fact the Mersey Dee Alliance area shares a £17 Billion economy he said: “The Mersey Dee Alliance has highlighted the interdependence between North East Wales and North West England, the only part of the UK with a contiguous urban area divided by a National Boundary.
“The pensions of almost 650,000 people in Wales are guaranteed by the UK Welfare System, 85% of private sector employees in Wales are employed by UK owned companies and 138 Million journeys take place each year across the border between England and Wales.
“Two thirds of the population of Wales live within 50 miles of that border.
“As I stated in May 2009 during the Welsh Conservative Debate on Cross Border issues. 'The border between England and Wales is long and porous and as a result, cross-border movements in health and education services are a long established fact of life- reflecting geographic and demographic realities … Devolution provides an opportunity for Wales to do things differently and for different approaches to be road-tested on either side of the border – but the objective must be to do things better rather than being different just for the sake of it. We must avoid at all costs a slate curtain in services between these two British Nations.
'Our long and porous border should be a cause for celebration and cooperation rather than an obstacle to efficiency and effectiveness'."
Mr Isherwood emphasised that Wales and the United Kingdom have a massively mutually beneficial relationship.
He said: “The global reputation of the United Kingdom is a powerful lever in attracting jobs and investment to Wales, while Wales’ continued presence in the union serves to enrich the entire UK, but the evolution of devolution is taking us to a crossroads.
“One direction could take us to separation, the other to a proud and confident Wales within a more federalised UK.”