Developmental gene expression redefines the mammalian brain stem

The study of developmental gene expression has exposed major errors in traditional representations of brain stem organization. The major misunderstandings concern the status of the isthmus, the pons, and the pretectal area. The isthmus is the most rostral segment of the hindbrain, separating the midbrain from the first rhombomere, whereas traditional schemes incorrectly consider the isthmus to be part of the midbrain. The basilar pons is developmentally restricted to rhombomeres 3 and 4, but human anatomy texts represent the “pons” (as distinct from “medulla oblongata”) as extending from the midbrain to rhombomere 7. The reason for this misunderstanding is that the basilar pons in humans spreads across the surface to cover large parts of the hindbrain. In the great majority of mammals, the basilar pons is clearly restricted to its original location in rhombomeres 3 and 4. The pretectal region, marked by the presence of the posterior commissure, has been arbitrarily classified as part of the midbrain for over a hundred years. Recent gene expression studies show that it belongs to the diencephalon and not to the midbrain. The human neuroanatomical and neurological literature has failed to take account of the evidence from developmental gene expression, and this will continue to handicap brain research and clinical neurology.