Homeobox gene expression in adult dorsal root ganglia during sciatic nerve regeneration: is regeneration a recapitulation of development?
After damage of the sciatic nerve, a regeneration process is initiated. Neurons in the dorsal root ganglion regrow their axons and functional connections. The molecular mechanisms of this neuronal regenerative process have remained elusive, but a relationship with developmental processes has been conceived. This chapter discusses the applicability of the developmental hypothesis of regeneration to the dorsal root ganglion; this hypothesis states that regeneration of dorsal root ganglion neurons is a recapitulation of development. We present data on changes in gene expression upon sciatic nerve damage, and the expression and function of homeobox genes. This class of transcription factors plays a role in neuronal development. Based on these data, it is concluded that the hypothesis does not hold for dorsal root ganglion neurons, and that regeneration-specific mechanisms exist. Cytokines and the associated Jak/STAT (janus kinase/signal transducer and activator of transcription) signal transduction pathway emerge as constituents of a regeneration-specific mechanism. This mechanism may be the basis of pharmacological strategies to stimulate regeneration.
Vogelaar
Christina F
CF
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Hoekman
Marco F M
MF
Gispen
Willem Hendrik
WH
Burbach
J Peter H
JP
D000818:Animals; D005727:Ganglia, Spinal / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology*; D006801:Humans; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism