PUBLICATION

Dynamic Polarization of Rab11a Modulates Crb2a Localization and Impacts Signaling to Regulate Retinal Neurogenesis

Authors
Clark, B.S., Miesfeld, J.B., Flinn, M.A., Collery, R.F., Link, B.A.
ID
ZDB-PUB-210227-6
Date
2021
Source
Frontiers in cell and developmental biology   8: 608112 (Journal)
Registered Authors
Clark, Brian, Collery, Ross, Link, Brian, Miesfeld, Joel B.
Keywords
Rab11, crumbs, endocytosis, interkinetic nuclear migration, neurogenesis, recycling endosome
Datasets
GEO:GSE154895
MeSH Terms
none
PubMed
33634099 Full text @ Front Cell Dev Biol
Abstract
Interkinetic nuclear migration (IKNM) is the process in which pseudostratified epithelial nuclei oscillate from the apical to basal surface and in phase with the mitotic cycle. In the zebrafish retina, neuroepithelial retinal progenitor cells (RPCs) increase Notch activity with apical movement of the nuclei, and the depth of nuclear migration correlates with the probability that the next cell division will be neurogenic. This study focuses on the mechanisms underlying the relationships between IKNM, cell signaling, and neurogenesis. In particular, we have explored the role IKNM has on endosome biology within RPCs. Through genetic manipulation and live imaging in zebrafish, we find that early (Rab5-positive) and recycling (Rab11a-positive) endosomes polarize in a dynamic fashion within RPCs and with reference to nuclear position. Functional analyses suggest that dynamic polarization of recycling endosomes and their activity within the neuroepithelia modulates the subcellular localization of Crb2a, consequently affecting multiple signaling pathways that impact neurogenesis including Notch, Hippo, and Wnt activities. As nuclear migration is heterogenous and asynchronous among RPCs, Rab11a-affected signaling within the neuroepithelia is modulated in a differential manner, providing mechanistic insight to the correlation of IKNM and selection of RPCs to undergo neurogenesis.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ka4TgTransgenic Insertion
    kca3TgTransgenic Insertion
      kca6TgTransgenic Insertion
        knu2TgTransgenic Insertion
          m289
            Point Mutation
            mw3TgTransgenic Insertion
              mw4TgTransgenic Insertion
                mw5TgTransgenic Insertion
                  mw6TgTransgenic Insertion
                    mw7TgTransgenic Insertion
                      1 - 10 of 28
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      crb2aMO2-crb2aMRPHLNO
                      tp53MO4-tp53MRPHLNO
                      1 - 2 of 2
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                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GFPEFGGFP
                      HyPerEFGHyPer
                      mCherryEFGmCherry
                      RFPEFGRFP
                      1 - 7 of 7
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                      Mapping
                      No data available