|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.
|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|
|PubMed:||27880902 Full text @ Cell Rep.|
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.
ABSTRACTLymphocytes 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.