Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways 
Regulating Early T Cell Development

Iwanami, Norimasa; Sikora, Katarzyna; Richter, Andreas S.; Mönnich, Maren; Guerri, Lucia; Soza-Ried, Cristian; Lawir, Divine-Fondzenyuy; Mateos, Fernando; Hess, Isabell; O’Meara, Connor P.; Schorpp, Michael; Boehm, Thomas

doi:10.1016/j.celrep.2016.11.003

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Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development

MPS-Authors

Iwanami, Norimasa
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sikora, Katarzyna
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Richter, Andreas S.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lawir, Divine-Fondzenyuy
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Mateos, Fernando
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hess, Isabell
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

O’Meara, Connor P.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Schorpp, Michael
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Boehm, Thomas
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S2211124716315236?via%3Dihub
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Citation

Iwanami, N., Sikora, K., Richter, A. S., Mönnich, M., Guerri, L., Soza-Ried, C., et al. (2016). Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development. Cell Reports, 17, 2259-2270. doi:10.1016/j.celrep.2016.11.003.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-AF88-4

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.