PUBLICATION

Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation

Authors
Ahmed, M., Kojima, Y., Masai, I.
ID
ZDB-PUB-220323-25
Date
2022
Source
eLIFE   11: (Journal)
Registered Authors
Ahmed, Mai Omar Abdulrahman, Kojima, Yutaka, Masai, Ichiro
Keywords
Jun, Strip1, apoptosis, developmental biology, migration, retinal ganglion cells, zebrafish
MeSH Terms
  • Animals
  • Retinal Ganglion Cells*/physiology
  • Retina
  • Apoptosis
  • Dendrites/physiology
  • Zebrafish*
(all 6)
PubMed
35314028 Full text @ Elife
Abstract
In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine (AC), and bipolar (BP) cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the striatin-interacting phosphatases and kinases (STRIPAK) complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. AC and BP cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin 3 (Strn3), and both show overlapping functions in RGC survival. Furthermore, loss of Strip1 or Strn3 leads to activation of the proapoptotic marker, Jun, within RGCs, and Jun knockdown rescues RGC survival in strip1 mutants. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.
Genes / Markers
Figures
Figure Gallery (19 images) / 2
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    		Complex
    kca4TgTransgenic Insertion
      oki8
        		Small Deletion
        oki029TgTransgenic Insertion
          oki067TgTransgenic Insertion
            oki068TgTransgenic Insertion
              oki069TgTransgenic Insertion
                q16bTgTransgenic Insertion
                  rw021TgTransgenic Insertion
                    rw147
                      		Point Mutation
                      1 - 10 of 12
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      atoh7MO1-atoh7MRPHLNO
                      junMO2-junMRPHLNO
                      strip1CRISPR1-strip1CRISPR
                      strip1MO1-strip1MRPHLNO
                      strn3MO1-strn3MRPHLNO
                      1 - 5 of 5
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GFPEFGGFP
                      mCherryEFGmCherry
                      YFPEFGYFP
                      1 - 5 of 5
                      Show
                      Mapping
                      No data available
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                      Citation
                      Ahmed, M., Kojima, Y., Masai, I. (2022) Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation. eLIFE. 11:.