About this item:

135 Views | 128 Downloads

Author Notes:

Correspondence: Eldon E. Geisert, egeiser@emory.edu

Author contributions: FS and EG conceived the study in coordination with AE.

JW performed all ONC procedures.

YL was responsible for intravitreal injections.

RK assisted with surgeries and animal breeding and isolated RNA for all samples.

OM and AE conducted SCN and DRG isolation.

FS performed and analyzed all ddPCR reactions and RACE assays, compiled figures and wrote the paper with input from EG and AE.

All authors read and approved the final manuscript.

We want to thank Oskar Laur for help with cloning and Xinping Huang for her assistance in virus packaging as well as April B. Still and Micah Chrenek for mouse colony management.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This study was supported by NEI grants R01EY017841 (EG), P30EY06360 (Emory Vision Core, P. Michael Iuvone), NINDS Grant NS057190 (AE), Unrestricted Funds from Research to Prevent Blindness and Department of Defense (DoD) Grant W81XWH12-1-0255 (EG).

FS is supported by the institutional training grant T32EY007092-30 (P. Michael Iuvone, PI).

The project was supported in part by the Viral Vector Core of the Emory Neuroscience NINDS Core Facilities grant, P30NS055077, and in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine as one of the Emory Integrated Core Facilities.

Additional support was provided by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • axon injury
  • axon regeneration
  • gene expression
  • retinal ganglion cells
  • DRG neurons
  • glaucoma
  • epigenetic regulation
  • untranslated regions
  • CORTICOSPINAL TRACT AXONS
  • TRANSCRIPTION FACTORS
  • SPINAL-CORD
  • REVERSE TRANSCRIPTION
  • GENE
  • CELLS
  • MOUSE
  • INHIBITION
  • PROTEINS
  • GLAUCOMA

Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems

Journal Title:

Frontiers in Molecular Neuroscience

Volume:

Volume 10

Publisher:

, Pages 354-354

Type of Work:

Article | Final Publisher PDF

Abstract:

In both the central nervous system (CNS) and the peripheral nervous system (PNS), axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i) the acutely injured CNS (retina after optic nerve crush) and PNS (dorsal root ganglion after sciatic nerve crush), (ii) a CNS regeneration model (retina after optic nerve crush and induced regeneration); and (iii) the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model). We find an initial increase of Sox11 in both PNS and CNS after injury; however, the expression of Bdnf isoforms is higher in the PNS relative to the CNS. Sustained upregulation of Sox11 is seen in the injured retina following regeneration treatment, while the expression of two Bdnf mRNA isoforms is suppressed. Furthermore, two isoforms of Sox11 with different 3'UTR lengths are present in the retina, and the long isoform is specifically upregulated in later stages of glaucoma. These results provide insight into the molecular cascades active during axonal injury and regeneration in mammalian neurons.

Copyright information:

© 2017 Struebing, Wang, Li, King, Mistretta, English and Geisert.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote