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
  • Animals
  • CRISPR-Cas Systems
  • Escherichia coli/immunology*
  • Escherichia coli/physiology
  • Escherichia coli Infections/genetics
  • Escherichia coli Infections/immunology*
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/immunology*
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Cellular
  • Immunity, Innate
  • Macrophages/immunology
  • Macrophages/metabolism
  • Macrophages/microbiology
  • Mutagenesis
  • Neutrophils/immunology
  • Neutrophils/metabolism
  • Neutrophils/microbiology
  • Transcriptional Activation
  • Zebrafish/genetics
  • Zebrafish/immunology*
  • Zebrafish/microbiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology*
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
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping