ZFIN ID: ZDB-PUB-161124-3
Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development
Iwanami, N., Sikora, K., Richter, A.S., Mönnich, M., Guerri, L., Soza-Ried, C., Lawir, D.F., Mateos, F., Hess, I., O'Meara, C.P., Schorpp, M., Boehm, T.
Date: 2016
Source: Cell Reports   17: 2259-2270 (Journal)
Registered Authors: Boehm, Tom, Hess, Isabell, Monnich, Maren, Schorpp, Michael
Keywords: T cell development, genetic screen, immunodeficiency, mouse, pre-mRNA splicing, zebrafish
Microarrays: GEO:GSE77480
MeSH Terms:
  • Alternative Splicing/genetics
  • Animals
  • Epistasis, Genetic
  • Gene Expression Regulation, Developmental
  • Genetic Testing*
  • Larva/genetics
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation/genetics
  • Organ Specificity/genetics
  • RNA Precursors/genetics*
  • RNA Precursors/metabolism
  • RNA Processing, Post-Transcriptional/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Ribonucleoproteins, Small Nuclear/metabolism
  • T-Lymphocytes/cytology*
  • T-Lymphocytes/metabolism*
  • Transcriptome/genetics
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • beta Karyopherins/deficiency
  • beta Karyopherins/metabolism
PubMed: 27880902 Full text @ Cell Rep.
Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication and/or repair pathways known from studies of immunocompromised mammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, genes encoding proteins required for pre-mRNA processing were enriched in the collection of mutants identified here. In both zebrafish and mice, deficiency of the splice regulator TNPO3 impairs intrathymic T cell differentiation, illustrating the evolutionarily conserved and cell-type-specific functions of certain pre-mRNA-processing factors for T cell development.