<P> Axon branches retract in a distal to proximal manner . The axonal contents that are retracted are thought to be recycled to other parts of the axon . The biological mechanism with which axonal pruning occurs still remains unclear for the mammalian central nervous system . However, pruning has been associated with guidance molecules in mice . Guidance molecules serve to control axon pathfinding through repulsion, and also initiate pruning of exuberant synaptic connections . Semaphorin ligands and the receptors neuropilins and plexins are used to induce retraction of the axons to initiate hippocampo - septal and infrapyramidal bundle (IPB) pruning . Stereotyped pruning of the hippocampal projections have been found to be significantly impaired in mice that have a Plexin - A3 defect . Specifically, axons that are connected to a transient target will retract once the Plexin - A3 receptors are activated by class 3 semaphorin ligands . In IPB, the expression of mRNA for Sema3F is present in the hippocampus prenatally, lost postnatally and returns in the stratum oriens . Coincidentally, onset IPB pruning occurs around the same time . In the case of the hippocampal - septal projections, expression of mRNA for Sema3A was followed by the initiation of pruning after 3 days . This suggests that pruning is triggered once the ligand reaches threshold protein levels within a few days after detectable mRNA expression . Pruning of axons along the visual corticospinal tract (CST) is defective in neuropilin - 2 mutants and plexin - A3 and plexin - A4 double mutant mice . Sema3F is also expressed in the dorsal spinal cord during the pruning process . There is no motor CST pruning defect observed in these mutants . </P> <P> Stereotyped pruning has also been observed in the tailoring of overextended axon branches from the retinotopy formation . Ephrin and the ephrin receptors, Eph, have been found to regulate and direct retinal axon branches . Forward signaling between Ephrin - A and EphA, along the anterior - posterior axis, has been found to inhibit retinal axon branch formation posterior to a terminal zone . The forward signaling also promotes pruning of the axons that have reached into the terminal zone . However, it remains unclear whether the retraction mechanism seen in IPB pruning is applied in retinal axons . </P> <P> Reverse signaling between ephrin - B proteins and their Eph receptor tyrosine kinases have been found to initiate the retraction mechanism in the IPB . Ephrin - B3 is observed to transduce tyrosine phosphorylation - dependent reverse signals into hippocampal axons that trigger pruning of excessive IPB fibers . The proposed pathway involves EphB being expressed on the surface of target cells that results in tyrosine phosphorylation of Ephrin - B3 . Ensuing binding of Ephrin - B3 to the cytoplasmic adaptor protein, Grb4, leads to the recruitment and binding of Dock180 and p21 activated kinases (PAK). The binding of Dock180 increases Rac - GTP levels, and PAK mediates the downstream signaling of active Rac that leads to the retraction of the axon and eventual pruning . </P> <P> Time - lapse imaging of retreating axons in neuromuscular junctions of mice have shown axonal shedding as a possible mechanism of pruning . The retreating axon moved in a distal to proximal order and resembled retraction . However, there were many cases in which remnants were shed as the axons were retracting . The remnants, named axosomes, contained the same organelles seen in the bulbs attached to the end of axons and were commonly found around the proximity of the bulbs . This indicates that axosomes are derived from the bulbs . Furthermore, axosomes did not have electron - dense cytoplasms or disrupted mitochondria indicating that they were not formed through Wallerian degeneration . </P>

When does neural pruning in the frontal lobes begin