A TRANSCRIPTION-DEPENDENT SWITCH CONTROLS COMPETENCE OF ADULT NEURONSFOR DISTINCT MODES OF AXON GROWTH

Although maturing neurons undergo a precipitous decline in the express ion of genes associated with developmental axon growth, structural cha nges in axon arbors occur in the adult nervous system under both norma l and pathological conditions. Furthermore, some neurons support exten sive regrowth of long axons after nerve injury. Analysis of adult dors al root ganglion (DRG) neurons in culture now shows that competence fo r distinct types of axon growth depends on different patterns of gene expression. In the absence of ongoing transcription, newly isolated ne urons can extend compact, highly branched arbors during the first day in culture. Neurons subjected to peripheral axon injury 2-7 d before p lating support a distinct mode of growth characterized by rapid extens ion of long, sparsely branched axons. A transition from ''arborizing'' to ''elongating'' growth occurs in naive adult neurons after similar to 24 hr in culture but requires a discrete period of new transcriptio n after removal of the ganglia from the intact animal. Thus, periphera l axotomy-by nerve crush or during removal of DRGs-induces a transcrip tion-dependent change that alters the type of axon growth that can be executed by these adult neurons. This transition appears to be trigger ed, in large part, by interruption of retrogradely transported signals , because blocking axonal transport in vivo can elicit competence for elongating growth in many DRG neurons. In contrast to peripheral axoto my, interruption of the centrally projecting axons of DRG neurons in v ivo leads to subsequent growth in vitro that is intermediate between ' 'arborizing'' and ''elongating'' growth. This suggests that the transi tion between these two modes of growth is a multistep process and that individual steps may be regulated separately. These observations toge ther suggest that structural remodeling in the adult nervous system ne ed not involve the same molecular apparatus as long axon growth during development and regeneration.