Dataset Information

DOWNREGULATION OF SPLICING REGULATOR RBFOX1 COMPROMISES VISUAL DEPTH PERCEPTION

ABSTRACT: Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder, and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) as well as in certain subsets of amacrine cells (ACs) within the inner nuclear and ganglion cell layers. In developing retinas, Rbfox1 can be detected as early as E12. At that age, Rbfox1 is localized in the cytoplasm of differentiated RGCs. Between P0 and P5, strong expression of Rbfox1 in the inner plexiform layer was observed. This coincided with switching of Rbfox1 localization in RGC somas from cytoplasmic to a predominantly nuclear. Dynamic changes in Rbfox1 expression during first 10 postnatal days are correlated with the stage II spontaneous retinal waves of excitation, which in mice begins around the time of birth and continues for as long as two weeks. By P10, dendritic staining of Rbfox1 was dramatically reduced and remained so in the fully developed retina. In Rbfox1 knockout (KO) animals no detectable changes in retinal gross morphology were observed two months after Rbfox1 downregulation. However, the visual cliff test revealed marked abnormalities of depth perception of these animals. Retinal transcriptome analysis of Rbfox1 KO mice identified a number of genes that are involved in establishing neural circuits and synaptic transmission, including Vamp1, Vamp2, Snap25, Trak2, and Slc1A7, suggesting a role of Rbfox1 in the regulation of genes that facilitate AC and RGC synaptic communication.

ORGANISM(S): Mus musculus

PROVIDER: GSE105084 | GEO | 2018/07/19

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:To investigate the retinal proteins associated with primary and secondary retinal ganglion cell (RGC) degeneration and explore their molecular pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in various retinal locations in response to localized optic nerve injury. Unilateral partial optic nerve transection (pONT) was performed on adult Wistar rats and their retinas were harvested at 2 weeks later. To confirm the separation of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicing (RBPMS) and glial fibrillary acidic protein (GFAP) was performed on retinal whole-mounts. Retinal proteomes in the temporal and nasal quadrants were evaluated with high resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and their expression was compared to the corresponding retinal quadrant in contralateral control eyes and further validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (p<0.05, FDR<1%) were quantified by SWATH-MS. Bioinformatics data analysis showed that there were 35 up-regulated and 24 down-regulated proteins in the temporal quadrant while 19 and 5 proteins were up-regulated and down-regulated, respectively, in the nasal quadrant respectively (n=4, p<0.05; fold change ≥1.4 fold or ≤0.7). Six proteins were regulated in both the temporal and the nasal quadrants including CLU, GFAP, GNG5, IRF2BPL, L1CAM and CPLX1. Linear regression analysis indicated a strong association between the data obtained by SWATH-MS and MRM-MS (temporal, R2=0.97; nasal, R2=0.96). Gene ontology analysis reveals statistically significant changes in the biological processes and cellular components of primary RGC degeneration. The majority of the significant changes in structural, signaling, and cell death proteins were associated with loss of RGCs in the area of primary RGC degeneration. The combined use of SWATH-MS and MRM-MS methods detects and quantifies regional changes of retinal protein expressions after localized injury. Future investigation with this integrated approach will significantly increase understanding of diverse processes of progressive RGC degeneration from a proteomic prospective.

Dataset Information

DOWNREGULATION OF SPLICING REGULATOR RBFOX1 COMPROMISES VISUAL DEPTH PERCEPTION

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure