The ability of postmitotic neurons to extend long axons is essential both to the establishment of neural circuitry during development, and to the regrowth of injured axons in adults. Axon elongation is generally confined to a period beginning

The ability of postmitotic neurons to extend long axons is essential both to the establishment of neural circuitry during development, and to the regrowth of injured axons in adults. Axon elongation is generally confined to a period beginning shortly after neurons undergo their final mitosis. Once mature synapses have been formed axon growth is sharply curtailed. Although most adult neurons lose the capacity to grow long axons, in some neurons this capacity can be regained following injury. It is not known whether the pathways that govern developmental axon growth and repression also control regenerative axon growth. One possibility is that injury reverses the diminished axon growth capacity of mature neurons by re-activating the developmental program. This hypothesis is supported by the fact that many growthassociated genes that are turned off in neurons during maturation are re-expressed during regeneration (reviewed by Skene, 1989). Alternatively, developmental growth and regenerative growth may have distinct requirements. Distinguishing between these two possibilities is crucial to our understanding of the intrinsic differences between neurons that are capable of regeneration and those that are not. Likely targets of the signaling pathways that regulate axon growth are genes encoding proteins that are abundant in axonal growth cones but absent from mature synapses. Expression of a number of such neuronal proteins, referred to as “growth associated proteins” (GAPs), is tightly correlated with axon growth during development and regeneration (reviewed by Skene, 1989). Expression of GAP genes is initiated in postmitotic neurons immediately prior to axon elongation, and is arrested subsequent to synapse formation. GAP gene expression can be reinitiated in response to injury in neurons undergoing regenerative growth. Given this tight correlation, it appears that signaling pathways that regulate axon growth also regulate GAP gene expression. To investigate signaling pathways that regulate axon growth during development and regeneration, we have attempted to separate the targets of these pathways within the regulatory sequences of GAP genes. This work has focused on the 1175 Development 128, 1175-1182 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV1652