DEVELOPMENT OF THE SUPERIOR TEMPORAL NEOCORTEX IS ANOMALOUS IN TRISOMY-21

Trisomy 21 (Down syndrome) is the most common inherited form of mental retardation in the United States, however, the basis of impaired cogn ition is unknown. We have used recently developed stereological cell c ounting techniques to quantitatively examine the pattern of neuronal m igration and maturation in one neocortical area during gestation in no rmal development and in trisomy 21. Normal development of the cerebral cortex occurs in two general sequences: Beginning at approximately 7- 8 weeks gestation, migration of cells destined to become neurons resul ts in the accumulation of cells in the cortical mantle. This process i s largely complete by 20-21 weeks. Over the next 7-10 weeks an ''insid e-out'' differentiation into lamina of different neuronal densities oc curs. Our data suggest that the second phase of cortical development, the emergence of lamination, is both delayed and disorganized in triso my 21. The observed pattern of cortical maturation may reflect an abno rmality in axonal and dendritic arborization that subsequently subserv e the connectional and functional units underlying normal cognition.