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In the Mesozoic Era (252 to 66 million years ago) Appalachia was an island land mass separated from Laramidia to the west by the Western Interior Seaway. The seaway eventually shrank, divided across the Dakotas, and retreated towards the Gulf of Mexico and Hudson Bay. This left the island masses joined in the continent of North America as the Rocky Mountains rose.
From the Turonian age of the Late Cretaceous to the very beginning of the Paleocene, Appalachia was separated from the rest of North America. Because of this, its fauna was isolated, and developed very differently from the tyrannosaur and ceratopsian dominated fauna of the western part of North America, the geologist's "Laramidia". Due to few fossiliferous deposits and many of Appalachia's fossil formations being destroyed by the Pleistocene ice age, little is known about Appalachia. In addition, due to lack of interest in Appalachia, many fossils that have been found in Appalachia lie unstudied and remain in the inaccurate genera to which they were assigned in the days of E.D. Cope and O.C. Marsh. However, a few fossil sites, such as Ellisdale in New Jersey, have given us a glimpse into this forgotten world of paleontology.
In Cretaceous North America, the dominant predators were the tyrannosaurs, huge predatory theropods with proportionately massive heads built for ripping flesh from their prey. Tyrannosaurs were the dominant predators in Appalachia too, but rather than the massive tyrannosaurine tyrannosaurs, the dryptosaurs were the top predators of Appalachia. Rather than developing the huge heads and massive bodies of their kin, dryptosaurs had more in common with the basal tyrannosaurs like Dilong and Eotyrannus, having long arms with three fingers, a more lithe skull and body, and were not as large as the largest tyrannosaurids. Two genera of Appalachian dryptosaurs are known, Dryptosaurus and Appalachiosaurus. Though Ornithomimid bones have been reported from Appalachia, it is now believed that these are the bones of juvenile dryptosaurs.
Another common group of Appalachian dinosaurs were the hadrosaurs. While the fossil record shows a staggering variety of hadrosaur forms in Laramidia, hadrosaur remains for Appalachia show less diversity due to the relative scarcity of fossil beds. Many hadrosaurs are known from Appalachia, however, such as Lophorhothon, Hypsibema, and Hadrosaurus. The hadrosaur Claosaurus, known from a specimen which floated into the Interior Seaway and was found in Kansas, might also be from Appalachia, since it was found closer to the Appalachia side of the seaway and is unknown from Western North America. Hypsibema, over fifty feet long, was the titan among eastern hadrosaurs. The genus likely took the environmental niche occupied by large sauropods in other areas.
The nodosaurs, a group of large, herbivorous armored dinosaurs resembling armadillos, are another testament to Appalachia's difference from Laramidia. By the latest Cretaceous, nodosaurs were scarce in western North America, existing only in specialized forms like Edmontonia and Panoplosaurus. A number of nodosaur scutes have been found in eastern North America. Often the findings are not diagnostic enough to identify species, but the remains attest to a greater number of these armored dinosaurs in Appalachia.