4.3 Article

Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish

Journal

MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 43, Issue 4, Pages 370-383

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2010.01.004

Keywords

Retina; Retinal ganglion cell; Tubulin; KLF; Optic nerve; p27; Promoter

Categories

Funding

  1. Michigan Economic Development Corporation [MEDC 38]
  2. Life Sciences Corridor
  3. National Glaucoma Research
  4. NEI
  5. NIH
  6. NATIONAL EYE INSTITUTE [R01EY018132] Funding Source: NIH RePORTER

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We report that knockdown of the alpha 1 tubulin isoform Tubal a, but not the highly related Tuba1b, dramatically impedes nervous system formation during development and RGC axon regeneration following optic nerve injury in adults. Within the tuba la promoter, a G/C-rich element was identified that is necessary for tuba1a induction during RGC differentiation and optic axon regeneration. KLF6a and 7a, which we previously reported are essential for optic axon regeneration (Veldman et al., 2007), bind this G/C-rich element and transactivate the tuba1a promoter. In vivo knockdown of KLF6a and 7a attenuate regeneration-dependent activation of the endogenous tuba la and p27 genes. These results suggest tuba la expression is necessary for CNS development and regeneration and that KLF6a and 7a mediate their effects, at least in part, via transcriptional control of tuba1a promoter activity. (C) 2010 Elsevier Inc. All rights reserved.

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