Journal of Molecular Neuroscience

, Volume 26, Issue 1, pp 17–26

Axotomy-induced early down-regulation of POU-IV class transcription factors Brn-3a and Brn-3b in retinal ganglion cells

  • Jochen H. Weishaupt
  • Nikolaj Klöcker
  • Mathias Bähr
Original Article

Abstract

It has been proposed that neurons being exposed to proapoptotic stimuli undergo dedifferentiation, a process that can either allow for regeneration and axon regrowth or, if remaining incomplete, can force the cell to activate apoptotic pathways. A pivotal step in the differentiation program from neuronal precursor cells to differentiated, postmitotic neurons is their exit from the cell cycle. The POU domain transcription factors Brn-3b and Brn-3a, which are expressed in retinal ganglion cells (RGCs) directly after the exit of RGC precursors from the cell cycle, can be employed as RGC-specific differentiation markers to study potential dedifferentiation of RGCs after axotomy. Here, we examined mRNA and protein expression of Brn-3a and-3b in rat RGCs following axonal lesion. We observed a rapid down-regulation of Brn-3a and -3b protein expression in axotomized RGCs, clearly preceding apoptosis of RGCs. Using real-time PCR, we show that regulation of Brn-3 expression occurred at the transcriptional level. The small subset of RGCs regenerating into a peripheral nerve graft did not (re-)express Brn-3a or -b. In conclusion, we found further evidence supporting the hypothesis of a dedifferentiation process in severed mature neurons. As Brn-3b expression has been shown to be a prerequisite for developmental survival of most RGCs and Brn-3a activates transcription of anti-apoptotic genes, down-regulation of Brn-3 transcription factors might be causally involved in the secondary death of adult RGCs following axotomy.

Index Entries

RGCs axotomy optic nerve transection Brn-3 neuronal apoptosis transcription factors 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Jochen H. Weishaupt
    • 1
  • Nikolaj Klöcker
    • 2
  • Mathias Bähr
    • 1
  1. 1.Department of NeurologyUniversity of GöttingenGöttingenGermany
  2. 2.Department of PhysiologyUniversity of FreiburgFreiburgGermany

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