title: Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development.
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.
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwanami
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany; Bioinformatics Unit, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sikora
authors.affiliation: Bioinformatics Unit, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Richter
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Mönnich
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Guerri
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Cristian
authors.initials: C
authors.lastname: Soza-Ried
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Divine-Fondzenyuy
authors.initials: DF
authors.lastname: Lawir
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Fernando
authors.initials: F
authors.lastname: Mateos
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Hess
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Connor P
authors.initials: CP
authors.lastname: O'Meara
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schorpp
authors.affiliation: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany. Electronic address: boehm@immunbio.mpg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D005820:Genetic Testing; D007814:Larva / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000172:deficiency / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger; D017411:Ribonucleoproteins, Small Nuclear; D029961:Zebrafish Proteins; D028961:beta Karyopherins
keywords: T cell development; genetic screen; immunodeficiency; mouse; pre-mRNA splicing; zebrafish