The morphology and phased outgrowth of callosal axons in the fetal rat.

The growth of axons of the corpus callosum was studied in fetal and early postnatal rats by means of anterograde and retrograde transport of horseradish peroxidase (HRP) applied to the developing cerebral cortex in the frontal and presumptive sensory motor regions. In the sensorimotor regions, the first axons to reach the midline at E18 arise from two separated groups of cells situated medially near the superior sagittal sinus and laterally just above the rhinal sulcus. Each group forms a stratum just beneath the cortical plate. Axons from cells in intervening regions arrive at the midline approximately one day later. By the first postnatal day (P0), a second stratum of callosally projecting cells can be identified superficial to the first. Callosal axons grow out from this stratum in the same sequence as those from the deeper stratum, axons from medial and lateral regions preceding those from intervening regions. [3H]thymidine labeling of animals later injected with HRP, indicates that callosal cells in the deep stratum enter their final mitosis at E15 and those in the superficial stratum at E16. Growing callosal axons have identifiable growth cones and filopodia at their tips but, as far as they could be traced, the axons do not branch. They grow orthogonal to radial glial processes of the cerebral hemisphere and diverge early from simultaneously outgrowing corticofugal axons directed to subcortical sites, as though following separate cues. Callosal axons advancing from one side grow directly into the path taken by those advancing from the other side.