The Benefits of Adding Insult to Injury

at the synapse. Regardless of the final explanation for readily grow in vivo into an implanted graft of PNS tissue the unexpected results with LAT, genetics has served (Richardson et al., 1980; David and Aguayo, 1981). its purpose in calling attention to a molecule that is not An environment favorable to regeneration, however, a usual suspect at the synapse. is not all that is needed. Further work showed that a How, in the end, should we think about the learning primary lesion in the peripheral branch of the dorsal root phenotype of latheo mutants? Is it a result of defective ganglion (DRG), followed by a second lesion in the spinal mushroom body development, impaired synaptic plas-branch of the same nerve at the same time or weeks ticity, or both? A satisfying answer must await the identi-later, results in more extensive growth into peripheral fication of mutants that separate the roles of lat at the nerve grafts situated in the dorsal columns. The condi-chromosome and the synapse, or the creation of conditioning peripheral nerve lesion somehow encourages tional mutants that rescue only the developmental de-growth for the majority of lesioned spinal axons to the fects. In the meantime, these two papers in Neuron may most distal edge of the graft but still not into the host inspire neurobiologists to head to the library for a re-CNS tissue beyond. In spite of the conditioning lesion fresher course on DNA replication. effect, it appears that a glial scar at the graft–host border , along with myelin-specific inhibitors, ultimately halts axonal growth (Richardson and Issa, 1984; Oudega Aaron DiAntonio et al., 1994). What is notable about these animal experi-Department of Molecular and Cell Biology ments is that the CNS axons grow better if their periph-and Woolf (1999) extend these observations by demonstrating that transected dorsal column axons regenerate 795–801. is, by all previous criteria, the highly nonpermissive environment of the damaged spinal cord (see figure). After corticospinal tract lesions by Schwab and colleagues, regeneration also occurred over relatively long distances , but these studies employed the monoclonal an-tibody IN-1, which neutralizes some of the myelin-specific inhibitors of regeneration (Bregman et al., 1995). In the study reported here, regeneration occurred without blocking myelin or glial scar inhibitors. Transecting the dorsal column and simultaneously lesioning the periph-A persistent, central question in neurobiology is, why eral nerve results in extensive regeneration into the le-do the axons of …