First Author | Iwanami N | Year | 2016 |
Journal | Cell Rep | Volume | 17 |
Issue | 9 | Pages | 2259-2270 |
PubMed ID | 27880902 | Mgi Jnum | J:240645 |
Mgi Id | MGI:5888832 | Doi | 10.1016/j.celrep.2016.11.003 |
Citation | Iwanami N, et al. (2016) Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development. Cell Rep 17(9):2259-2270 |
abstractText | 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. |