Long-distance axon growth ability of corticospinal neurons is lost in a segmentally-distinct manner

The neonatal central nervous system (CNS) in mammals is known to support greater regeneration than the adult CNS. Established models of neonatal CNS injuries cause significant disruption to the microenvironments needed for axon growth and guidance. This limits their ability to investigate long-distance axon growth ability. We established a novel microsurgical approach to transect developing corticospinal neuron (CSN) axons, without producing an overt spinal lesion and investigated long-distance growth ability of the developing corticospinal tract (CST) in neonatal mice. We identified, rather surprisingly, that this ability is not equivalently lost at distinct spinal levels. At postnatal day 4 (P4), while this ability is robustly maintained at thoracic T11, it is completely abolished at cervical C2. We further identify that thoraco-lumbar-projecting CSN lose growth ability at cervical C2 even while extending axons to thoraco-lumbar segments. Further, long-distance regrowth is possible even when CSN axons are displaced from their “normal” location in the dorsal funiculus to the dorsolateral funiculus, where only a minority of the CST normally traverses. The differential loss of long-distance growth at distinct spinal levels does not appear to be due to segmental differences in astrocytic or microglial activation. Our results suggest that the initial control over long-distance axon growth is differentially governed across the length of an axon by context-specific mechanisms.