Zebrafish mutants with disrupted early T-cell and thymus development identified in early pressure screen

Dev Dyn. 2008 Sep;237(9):2575-84. doi: 10.1002/dvdy.21683.


Generation of mature T lymphocytes requires an intact hematopoietic stem cell compartment and functional thymic epithelium. We used the zebrafish (Danio rerio) to isolate mutations that affect the earliest steps in T lymphopoiesis and thymic organogenesis. Here we describe the results of a genetic screen in which gynogenetic diploid offspring from heterozygous females were analyzed by whole-mount in situ hybridization for the expression of rag-1. To assess immediately if a global defect in hematopoiesis resulted in the mutant phenotype, alpha-embryonic globin expression was simultaneously assayed for multilineage defects. In this report, we present the results obtained with this strategy and show representative mutant phenotypes affecting early steps in T-cell development and/or thymic epithelial cell development. We discuss the advantage of this strategy and the general usefulness of the zebrafish as a model system for vertebrate lymphopoiesis and thymic organogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Branchial Region / embryology
  • Branchial Region / metabolism
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology
  • Homeodomain Proteins / genetics
  • Ikaros Transcription Factor / genetics
  • In Situ Hybridization
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / metabolism*
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics


  • Forkhead Transcription Factors
  • Foxn1 protein, zebrafish
  • Homeodomain Proteins
  • Zebrafish Proteins
  • ikzf1 protein, zebrafish
  • RAG-1 protein
  • Ikaros Transcription Factor