PUBLICATION

RhoA GEF Mcf2lb regulates rosette integrity during collective cell migration

Authors
Olson, H.M., Maxfield, A., Calistri, N.L., Heiser, L.M., Qian, W., Knaut, H., Nechiporuk, A.V.
ID
ZDB-PUB-240103-24
Date
2024
Source
Development (Cambridge, England)   151(1): (Journal)
Registered Authors
Knaut, Holger, Nechiporuk, Alex, Olson, Hannah
Keywords
Apical constriction, Cell migration, Rosette morphogenesis, Sensory development, Zebrafish lateral line
Datasets
GEO:GSE229567
MeSH Terms
  • Signal Transduction/physiology
  • Zebrafish Proteins/metabolism
  • Lateral Line System*
  • Cell Movement/genetics
  • Morphogenesis/physiology
  • Animals
  • Zebrafish*/metabolism
(all 7)
PubMed
38165177 Full text @ Development
Abstract
Multicellular rosettes are transient epithelial structures that serve as important cellular intermediates in the formation of diverse organs. Using the zebrafish posterior lateral line primordium (pLLP) as a model system, we investigated the role of the RhoA GEF Mcf2lb in rosette morphogenesis. The pLLP is a group of ∼150 cells that migrates along the zebrafish trunk and is organized into epithelial rosettes; these are deposited along the trunk and will differentiate into sensory organs called neuromasts (NMs). Using single-cell RNA-sequencing and whole-mount in situ hybridization, we showed that mcf2lb is expressed in the pLLP during migration. Live imaging and subsequent 3D analysis of mcf2lb mutant pLLP cells showed disrupted apical constriction and subsequent rosette organization. This resulted in an excess number of deposited NMs along the trunk of the zebrafish. Cell polarity markers ZO-1 and Par-3 were apically localized, indicating that pLLP cells are properly polarized. In contrast, RhoA activity, as well as signaling components downstream of RhoA, Rock2a and non-muscle Myosin II, were diminished apically. Thus, Mcf2lb-dependent RhoA activation maintains the integrity of epithelial rosettes.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
mcf2lbnl25/nl25; sk115Tg/sk115Tg; zf106Tg/zf106Tgstandard conditionsProtruding-mouth
mcf2lbnl25/nl25; sk115Tg/sk115Tg; zf106Tg/zf106Tgstandard conditionsProtruding-mouth
mcf2lbnl25/nl25; sk115Tg/sk115Tg; zf106Tg/zf106Tgstandard conditionsProtruding-mouth
mcf2lbnl25/nl25; sk122Tg/sk122Tg; sk85Tg/sk85Tgstandard conditionsPrim-25
mcf2lbnl25/nl25; sk122Tg/sk122Tg; sk85Tg/sk85Tgstandard conditionsPrim-25
mcf2lbnl25/nl25; zf106Tg/zf106Tgstandard conditionsPrim-15
mcf2lbnl25/nl25; zf106Tg/zf106Tgstandard conditionsPrim-15
mcf2lbnl25/nl25; zf106Tg/zf106Tgstandard conditionsPrim-15
mcf2lbnl25/nl25; zf106Tg/zf106Tgstandard conditionsHigh-pec
mcf2lbnl25/nl25; zf106Tg/zf106Tgstandard conditionsHigh-pec
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nl25
    Complex
    nl26
      Complex
      sk85TgTransgenic Insertion
        sk115TgTransgenic Insertion
          sk122TgTransgenic Insertion
            zf106TgTransgenic Insertion
              zf668TgTransgenic Insertion
                1 - 7 of 7
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                mcf2lbCRISPR1-mcf2lbCRISPR
                mcf2lbCRISPR2-mcf2lbCRISPR
                mcf2lbCRISPR3-mcf2lbCRISPR
                1 - 3 of 3
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                Fish
                Antibodies
                Name Type Antigen Genes Isotypes Host Organism
                Ab1-myl-Ser19-Ppolyclonal
                  Rabbit
                  Ab1-rock2apolyclonal
                    IgG1Rabbit
                    Ab1-tjp1monoclonalIgG1Mouse
                    1 - 3 of 3
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                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    mScarletEFGmScarlet
                    CFPEFGCFP
                    DsRedEFGDsRed
                    EGFPEFGEGFP
                    mCherryEFGmCherry
                    sfGFPEFGsfGFP
                    1 - 6 of 6
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                    Mapping
                    No data available