PUBLICATION

Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis

Authors
Clark, B.S., Cui, S., Miesfeld, J.B., Klezovitch, O., Vasioukhin, V., and Link, B.A.
ID
ZDB-PUB-120702-2
Date
2012
Source
Development (Cambridge, England)   139(9): 1599-1610 (Journal)
Registered Authors
Clark, Brian, Cui, Shuang Alice, Link, Brian, Miesfeld, Joel B.
Keywords
neurogenesis, notch, zebrafish, lethal giant larvae, Shroom3, interkinetic nuclear migration, cell polarity
MeSH Terms
  • Bromodeoxyuridine
  • Time-Lapse Imaging
  • Animals
  • Neuroepithelial Cells/metabolism*
  • Oligonucleotides/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Cell Cycle Proteins/deficiency*
  • Cell Cycle Proteins/metabolism
  • Neurogenesis/physiology*
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/metabolism
  • Retina/cytology*
  • Receptors, Notch/metabolism*
  • Microfilament Proteins/metabolism
(all 15)
PubMed
22492354 Full text @ Development
Abstract

To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric cell division, cell shape and cell cycle exit. We found that vertebrate retinal neuroepithelia deficient for Llgl1 retained overt apicobasal polarity, but had expanded apical domains. Llgl1 retinal progenitors also had increased Notch activity and reduced rates of neurogenesis. Blocking Notch function by depleting Rbpj restored normal neurogenesis. Experimental expansion of the apical domain, through inhibition of Shroom3, also increased Notch activity and reduced neurogenesis. Significantly, in wild-type retina, neurogenic retinal progenitors had smaller apical domains compared with proliferative neuroepithelia. As nuclear position during interkinetic nuclear migration (IKNM) has been previously linked with cell cycle exit, we analyzed this phenomenon in cells depleted of Llgl1. We found that although IKNM was normal, the relationship between nuclear position and neurogenesis was shifted away from the apical surface, consistent with increased pro-proliferative and/or anti-neurogenic signals associated with the apical domain. These data, in conjunction with other findings, suggest that, in retinal neuroepithelia, the size of the apical domain modulates the strength of polarized signals that influence neurogenesis.

Genes / Markers
Figures
Figure Gallery (15 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kca6TgTransgenic Insertion
    knu2TgTransgenic Insertion
      knu3TgTransgenic Insertion
        mw3TgTransgenic Insertion
          mw21TgTransgenic Insertion
            mw22TgTransgenic Insertion
              mw43TgTransgenic Insertion
                rw021TgTransgenic Insertion
                  s356tTgTransgenic Insertion
                    y83TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      atoh7MO1-atoh7MRPHLNO
                      llgl1MO1-llgl1MRPHLNO
                      llgl1MO2-llgl1MRPHLNO
                      rbpjaMO4-rbpja,rbpjbMRPHLNO
                      rbpjbMO4-rbpja,rbpjbMRPHLNO
                      tp53MO4-tp53MRPHLNO
                      1 - 6 of 6
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                      Fish
                      Antibodies
                      Orthology
                      Gene Orthology
                      llgl1
                      llgl2
                      1 - 2 of 2
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                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      RFPEFGRFP
                      1 - 4 of 4
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                      Mapping
                      No data available