Gene expression profiling reveals that peripheral nerve regeneration is a conseq

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J Neurochem. 2006 Mar;96(5):1441-57.

Gene expression profiling reveals that peripheral nerve regeneration

is a consequence of both novel injury-dependent and reactivated

developmental processes.

Bosse F, Hasenpusch-Theil K, Kury P, Muller HW.

Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-

Heine-University, Dusseldorf, Germany.

One of the most striking features of the injured mature peripheral

nervous system is the ability to regenerate.

The lesioned peripheral nervous system displays stereotypic

histopathological reactions indicating the activation of a co-

ordinated lesion-induced gene expression programme.

Previous research has already identified molecular components of this

axonal switch from a mature transmitting to a regenerative growth

mode. The observed alterations in gene expression within the lesioned

distal nerve stump were largely attributed to recapitulated

developmental processes.

However, to our knowledge, this hypothesis has not been proven

systematically. Most of the stereotypic molecular and cellular

reactions during nerve development and repair can be assigned to

specific time windows. Consequently, we have compared gene expression

profiles of both paradigms at six different time-points each by means

of cDNA array hybridization.

Our data identified injury-specific molecular reactions and revealed

to what extent developmental mechanisms are reactivated in response

to nerve lesion. Ninety-one genes (47% of the regeneration-associated

genes) were found to be significantly regulated in both paradigms,

suggesting that regeneration only partially recapitulates development

and that approximately half of the regulated genes are part of a

regeneration-dependent programme.

Interestingly, mainly genes encoding signal transducers or factors

involved in processes such as cell death, immune response, transport

and transcriptional regulation showed injury-specific gene expression.