The natural barriers around the Fertile Crescent are the deserts and the mountains.
The people that migrated in the Fertile Crescent, in what is known as Mesopotamia, moved in there because it was the only place that had nice conditions for living and prosper. The Mesopotamia region was between two very big rivers, the Tigris and Euphrates rivers. These two rivers were flooding each year and creating a new very fertile soil, which allowed the people to be engaged in agriculture and have a stable food source, and also to have a stable fresh water source.
On the other hand, the deserts and the mountains, were not providing these condition. The deserts are too dry, there's not enough food and water, and life is extremely hard and has to be in a nomadic style. The mountains are very restrictive in what they offer and in how big of a part of the year. While the summers might be good and provide nice living conditions, the winters are very cruel and can bring death very easily.
