PUBLICATION
Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development
- Authors
- 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.
- ID
- ZDB-PUB-161124-3
- 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
- Datasets
- 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.
Citation
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. (2016) Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development. Cell Reports. 17:2259-2270.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping