Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiR-124 acts through coREST to control the onset of Sema3A sensitivity in navigating retinal growth cones

ABSTRACT: 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. 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.

ORGANISM(S): Xenopus laevis

SUBMITTER: Cei Abreu-Goodger

PROVIDER: E-GEOD-33444 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones.

Baudet Marie-Laure ML Zivraj Krishna H KH Abreu-Goodger Cei C Muldal Alistair A Armisen Javier J Blenkiron Cherie C Goldstein Leonard D LD Miska Eric A EA Holt Christine E CE

Nature neuroscience 20111204 1

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 ...[more]

PMID: 22138647

Similar Datasets

Project description:The loss of cone photoreceptor cells, which are critical for optimal daylight vision, have the great impact on vision during retinal degenerations. Retinal differentiation of human induced pluripotent stem cell (hiPSC) sources could provide a renewable source of cone photoreceptors towards developing a cone cell replacement therapy to treat blindness. Demonstration of comparable gene expression profiles between human foetal and stem cell-derived cones at equivalent stages is required to progress the cell transplantation approach into the patient, as it is hypothesised stem cell-derived cones are required to show high levels of developmental recapitulation of the in vivo generated cones. In this study, the AAV2/9.pR2.1.GFP reporter was used to specifically label L/M-opsin cone photoreceptors in human foetal retinal samples, obtained from the MRC-Wellcome Trust Human Developmental Biology Resource, at a range of developmental stages. The L/M-opsin cone population represent the majority cone cell types in the adult human retina and are the only photoreceptors present within the fovea. Using fluorescence activated cell sorting, L/M-opsin GFP+ cones and GFP- retinal populations, alongside total foetal retinal samples containing all retinal cell tytpes, were isolated and processed for bulk RNA sequencing and downstream comparative analysis. Using DESeq2 differential gene expression analyses, statistically significant genes enriched within the GFP+ human foetal LM-opsin cone populations were determined which led to the identification of a cone enriched gene signature of human L/M-opsin cone photoreceptors. The AAV2/9.pR2.1.GFP reporter was applied to hiPSC-derived retinal cultures to isolate and process cone-like cell populations for RNA sequencing using the same strategy developed within the human foetal retina. Applying the cone enriched gene signature to the transcriptome of hiPSC-derived GFP+ samples at equivalent developmental stages revealed some expression similarities in genes found to be enriched within the late foetal L/M-opsin cone photoreceptors. This analysis overall revealed an intermediate stage of cone differentiation was achieved within the hiPSC-derived samples and the comparison to human foetal L/M-opsin gene express profiles suggesting further differentiation of hiPSC-derived sample is required.

Dataset Information

MiR-124 acts through coREST to control the onset of Sema3A sensitivity in navigating retinal growth cones

Publications

miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure