PUBLICATION

Genetic analysis of zebrafish homologs of human FOXQ1, foxq1a and foxq1b, in innate immune cell development and bacterial host response

Authors
Earley, A.M., Dixon, C.T., Shiau, C.E.
ID
ZDB-PUB-180314-10
Date
2018
Source
PLoS One   13: e0194207 (Journal)
Registered Authors
Shiau, Celia
Keywords
none
MeSH Terms
  • Mutagenesis
  • CRISPR-Cas Systems
  • Host-Pathogen Interactions
  • Macrophages/immunology
  • Macrophages/metabolism
  • Macrophages/microbiology
  • Escherichia coli Infections/genetics
  • Escherichia coli Infections/immunology*
  • Immunity, Innate
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish/microbiology
  • Transcriptional Activation
  • Neutrophils/immunology
  • Neutrophils/metabolism
  • Neutrophils/microbiology
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/immunology*
  • Immunity, Cellular
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology*
  • Animals
  • Escherichia coli/immunology*
  • Escherichia coli/physiology
  • Humans
(all 25)
PubMed
29534099 Full text @ PLoS One
Abstract
FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs (foxq1a and foxq1b) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish. Using a combination of molecular, cellular, and embryological approaches, we characterized single and double foxq1a bcz11 and foxq1b bcz18 mutants. This study provides the first genetic mutant analyses of zebrafish foxq1a and foxq1b. Interestingly, we found that foxq1a, but not foxq1b, was transcriptionally regulated during a bacterial response, while the expression of foxq1a was detected in sorted macrophages and upregulated in foxq1a-deficient mutants. However, the transcriptional response to E. coli challenge of foxq1a and foxq1b mutants was not significantly different from that of their wildtype control siblings. Our data shows that foxq1a may have a role in modulating bacterial response, while both foxq1a and foxq1b are not required for the development of macrophages, neutrophils, and microglia. Considering the implicated role of FOXQ1 in a vast number of cancers and biological processes, the foxq1a and foxq1b null mutants from this study provide useful genetic models to further investigate FOXQ1 functions.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
foxq1abcz11/+standard conditionsDay 4
foxq1abcz11/bcz11standard conditionsPec-fin
foxq1abcz11/bcz11standard conditionsPec-fin
foxq1abcz11/bcz11standard conditionsPec-fin
foxq1abcz11/bcz11standard conditionsPec-fin
foxq1abcz11/bcz11standard conditionsDay 4
foxq1abcz11/bcz11standard conditionsDay 4
foxq1abcz11/bcz11standard conditionsDay 4
foxq1abcz11/bcz11standard conditionsDay 5
foxq1abcz11/bcz11standard conditionsDay 5
1 - 10 of 28
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
bcz11
    		Small Deletion
    bcz18
      		Indel
      gl22TgTransgenic Insertion
        sd2TgTransgenic Insertion
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          foxq1aCRISPR1-foxq1aCRISPR
          foxq1aCRISPR2-foxq1aCRISPR
          foxq1aCRISPR3-foxq1aCRISPR
          foxq1bCRISPR1-foxq1bCRISPR
          foxq1bCRISPR2-foxq1bCRISPR
          foxq1bCRISPR3-foxq1bCRISPR
          1 - 6 of 6
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          Fish
          Fish
          foxq1abcz11/bcz11
          foxq1abcz11/bcz11; foxq1bbcz18/bcz18
          foxq1abcz11/+
          foxq1bbcz18/bcz18
          foxq1bbcz18/+
          gl22Tg
          sd2Tg
          WT
          1 - 8 of 8
          Show
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRedEFGDsRed
          EGFPEFGEGFP
          1 - 2 of 2
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          Mapping
          No data available
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          Citation
          Earley, A.M., Dixon, C.T., Shiau, C.E. (2018) Genetic analysis of zebrafish homologs of human FOXQ1, foxq1a and foxq1b, in innate immune cell development and bacterial host response. PLoS One. 13:e0194207.