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

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

Resultado de la investigación: Article

6 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)2259-2270
Número de páginas12
PublicaciónCell Reports
Volumen17
N.º9
DOI
EstadoPublished - 22 nov 2016
Publicado de forma externa

Huella dactilar

T-cells
RNA Precursors
Zebrafish
T-Lymphocytes
Gene encoding
Mammals
Lymphocytes
Immune system
Processing
Vertebrates
Immune System
Repair
Transcription Factors
Cytokines
Mutation
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Citar esto

Iwanami, N., Sikora, K., Richter, A. S., Mönnich, M., Guerri, L., Soza-Ried, C., ... Boehm, T. (2016). Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development. Cell Reports, 17(9), 2259-2270. https://doi.org/10.1016/j.celrep.2016.11.003
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. / Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development. En: Cell Reports. 2016 ; Vol. 17, N.º 9. pp. 2259-2270.
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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.",
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Iwanami, N, Sikora, K, Richter, AS, Mönnich, M, Guerri, L, Soza-Ried, C, Lawir, DF, Mateos, F, Hess, I, O'Meara, CP, Schorpp, M & Boehm, T 2016, 'Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development', Cell Reports, vol. 17, n.º 9, pp. 2259-2270. https://doi.org/10.1016/j.celrep.2016.11.003

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.

En: Cell Reports, Vol. 17, N.º 9, 22.11.2016, p. 2259-2270.

Resultado de la investigación: Article

TY - JOUR

T1 - Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development

AU - Iwanami, Norimasa

AU - Sikora, Katarzyna

AU - Richter, Andreas S.

AU - Mönnich, Maren

AU - Guerri, Lucia

AU - Soza-Ried, Cristian

AU - Lawir, Divine Fondzenyuy

AU - Mateos, Fernando

AU - Hess, Isabell

AU - O'Meara, Connor P.

AU - Schorpp, Michael

AU - Boehm, Thomas

PY - 2016/11/22

Y1 - 2016/11/22

N2 - 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.

AB - 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.

KW - genetic screen

KW - immunodeficiency

KW - mouse

KW - pre-mRNA splicing

KW - T cell development

KW - zebrafish

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JF - Cell Reports

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