Pre- and post-mitotic events contribute to the progressive acquisition of area-specific connectional fate in the neocortex

The adult primary motor cortex (area 6) is characterized by a stronger proj ection to the spinal cord than the primary somatosensory cortex (area 3). H ere we have explored the progressive and regressive phenomena that determin e these areal differences in the number of corticospinal neurons (CSNs). CS Ns were birthdated with [H-3]thymidine and subsequently retrogradely labele d from the spinal cord. The time window of CSN production is identical in b oth areas. The probability that a cohort of neuroblasts project to the spin al cord is indicated by the percentage of [H-3]thymidine-positive neurons t hat can be back-labeled from the spinal cord. In the neonate this fate inde x is significantly higher in area 6 compared with area 3, indicating that e arly regionalization of cell fate contributes to areal differences in CSN n umber. In neonatal reeler mice, an increase in CSN number was accompanied b y an increased fate index, showing that the integrity of the post-mitotic e nvironment is required for the specification of the appropriate number of n eurons expressing a given connectional phenotype. Postnatal development in reeler and normal is characterized by an area-specific elimination of CSN a xons, which reduces areal differences in CSN number. These results show a p rogressive acquisition of CSN fate in the neocortex and indicate that both early regionalization and late environmental signals contribute to determin ing areal differences of connectional phenotype.