XB-ART-44540Nat Neurosci. December 4, 2011; 15 (1): 29-38.
miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones.
During axon pathfinding, growth cones commonly show changes in sensitivity to guidance cues that follow a cell-intrinsic timetable. The cellular timer mechanisms that regulate such changes are, however, poorly understood. Here we have investigated microRNAs (miRNAs) in the timing control of sensitivity to the semaphorin Sema3A in Xenopus laevis 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 (NRP1) receptor expression and caused cell-autonomous pathfinding errors. CoREST, a cofactor of a NRP1 repressor, was newly identified as a target and mediator of miR-124 for this highly specific temporal aspect of RGC growth cone responsiveness. Our findings indicate that miR-124 is important in regulating the intrinsic temporal changes in RGC growth cone sensitivity and suggest that miRNAs may act broadly as linear timers in vertebrate neuronal development.
PubMed ID: 22138647
PMC ID: PMC3661270
Article link: Nat Neurosci.
Grant support: 085314 Wellcome Trust , Medical Research Council , Wellcome Trust , 092096 Wellcome Trust , Medical Research Council , 11832 Cancer Research UK, 085314 Wellcome Trust , Wellcome Trust , CRUK_11832 Cancer Research UK, WT085314 Wellcome Trust , Medical Research Council , Wellcome Trust , WT092096 Wellcome Trust , 092096 Wellcome Trust , Medical Research Council , 11832 Cancer Research UK, 085314 Wellcome Trust , Wellcome Trust
Genes referenced: nrp1 sema3a