Research article
Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development
1 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK
2 Program in Molecular Medicine, University of Massachusetts Medical School, Plantation St, Worcester, MA 01605, USA
3 Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
4 Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, CB2 2PY, UK
5 Institut National de la Santé et de la Recherche Médicale, Biologie des Jonctions Neuromusculaires, Université Paris V, Paris, France
6 Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2 Academia Road, Taipei 11529, Taiwan
Neural Development 2009, 4:8 doi:10.1186/1749-8104-4-8
Published: 2 March 2009Abstract
Background
Translation in axons is required for growth cone chemotropic responses to many guidance cues. Although locally synthesized proteins are beginning to be identified, how specific mRNAs are selected for translation remains unclear. Control of poly(A) tail length by cytoplasmic polyadenylation element (CPE) binding protein 1 (CPEB1) is a conserved mechanism for mRNA-specific translational regulation that could be involved in regulating translation in axons.
Results
We show that cytoplasmic polyadenylation is required in Xenopus retinal ganglion cell (RGC) growth cones for translation-dependent, but not translation-independent, chemotropic responses in vitro, and that inhibition of CPE binding through dominant-negative interference severely reduces axon outgrowth in vivo. CPEB1 mRNA transcripts are present at low levels in RGCs but, surprisingly, CPEB1 protein was not detected in eye or brain tissue, and CPEB1 loss-of-function does not affect chemotropic responses or pathfinding in vivo. UV cross-linking experiments suggest that CPE-binding proteins other than CPEB1 in the retina regulate retinal axon development.
Conclusion
These results indicate that cytoplasmic polyadenylation and CPE-mediated translational regulation are involved in retinal axon development, but that CPEB1 may not be the key regulator of polyadenylation in the developing retina.
