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Forward genetic screens in zebrafish identify novel molecular 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/repair pathways known from studies of immuno-compromised mammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, certain pre-mRNA processing factor genes, including tnpo3, encoding a regulator of alternative splicing, were also found to play a specific role in early T cell development. In both zebrafish and mouse, TNPO3 deficiency impairs intrathymic T cell differentiation, illustrating evolutionarily conserved and cell type-specific functions of certain pre-mRNA processing factor.

ORGANISM(S): Danio rerio

PROVIDER: GSE77480 | GEO | 2016/11/28

SECONDARY ACCESSION(S): PRJNA310608

REPOSITORIES: GEO

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An evolutionarily conserved function of the pre-mRNA splicing regulator TNPO3 for T cell development

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