GEO Series: GSE33444
During axon pathfinding, growth cones commonly exhibit changes in sensitivity to guidance cues that follow a strict timetable, even in the absence of pathway feedback, implicating cell-intrinsic regulation. Cellular timer mechanisms, however, are poorly understood. Here we have investigated microRNAs in the timing control of Sema3A sensitivity in retinal ganglion cell (RGC) growth cones. A developmental profiling screen identified miR-124 as a candidate timer. Loss of miR-124 delayed the onset of Sema3A sensitivity and concomitant Neuropilin-1 (NRP-1) receptor expression, and caused cell autonomous pathfinding errors. CoREST, a cofactor of a NRP1 repressor, was identified as a novel target and mediator of miR-124 for this highly specific temporal aspect of RGC growth cone responsiveness. Our findings indicate that miR-124 plays an important role in regulating the intrinsic temporal changes in RGC growth cone sensitivity and suggest that microRNAs may play a broad role as linear timers in vertebrate neuronal development.
Contributors: Cei Abreu-Goodger, Marie-Laure Baudet, Krishna Zivraj, Alistair Muldal, Javier Armisen, Cherie Blenkiron, Leonard Goldstein, Erik Miska, Christine Holt
Experiment Type: Two independent experiments were performed. One with a single sample for each of 3 stages, and the second with 2 biological replicates of each stage.
Article: XB-ART-44540, PubMed
Source: NCBI GEO, Xenbase Download
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