Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish.
We report that knockdown of the alpha1 tubulin isoform Tuba1a, 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 tuba1a 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 tuba1a and p27 genes. These results suggest tuba1a 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.
Veldman
Matthew B
MB
Neuroscience Program, University of Michigan, Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Bemben
Michael A
MA
Goldman
Daniel
D
D000818:Animals; D030801:Animals, Genetically Modified; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020221:Optic Nerve Injuries / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
C525954:KLF6a protein, zebrafish; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014404:Tubulin; D029961:Zebrafish Proteins