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The city of Clayton, Missouri is the county seat of St. Louis County, and borders on the city of St. Louis. When St. Louis separated from St. Louis County in 1876, the county was left without a seat of government. County official selected a site that was donated for that purpose by Ralph Clayton and Martin Hanley. Clayton, for whom the new city was named, had come to Missouri from Virginia in the 1830s, settling in the southeastern part of what was to become the city that bears his name. Hanley had also come from Virginia, establishing a blacksmithing business, and building a home on the north side of town. In 1877, Clayton became the new county seat, and was incorporated as a city in 1913, largely to avoid annexation by University City. Neighborhoods within Clayton include Claverach Park, Clayton Gardens, Clayshire, DeMun, Davis Place, Hillcrest, Moorlands, Old Town, Downtown Clayton, Polo, Wydown Forest, Wydown Terrace, Forsyth, and Washington University. Clayton is surrounded by St. Louis to the east, University City to the northeast, Velda Village to the north, Ladue to the west, and Maplewood to the south. A study has been underway since 2006 to determine the efficacy of merging Richmond Heights with Clayton.

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