Activating Transcription Factor 3 and Regeneration

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Activating Transcription Factor 3 and Regeneration

http://www.medicalnewstoday.com/articles/77804.php

Injury of peripheral axons results in a regenerative response from

the central as well as the peripheral process of a dorsal root

ganglion (DRG) neuron. This " conditioning " effect is mediated by

altered transcription of multiple genes and involves both enhanced

axonal growth and reduced inhibition by myelin. Seijffers et al.

concentrated on the transcription factor ATF3 as a candidate

mediator of the enhanced growth because ATF3 is expressed after

peripheral, but not central, axonal injury. The authors generated

transgenic mice that expressed ATF3 constitutively in DRG neurons.

After sciatic nerve crush, ATF3 transgenic mice displayed early

nerve regeneration similar to wild-type (WT) mice after a

preconditioning lesion. Preconditioned WT mice extended axons into

the spinal cord after a dorsal column injury, but axons in ATF3

transgenic mice did not. Similarly, ATF3-expressing neurons were

unable to overcome myelin inhibition. Thus ATF by itself did not

completely recapitulate the benefits of preconditioning.

Authors: Rhona Seijffers, D. Mills, and Clifford J. Woolf