title: Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved.
abstract: The transcription factor c-myb has emerged as one of the key regulators of vertebrate hematopoiesis. In mice, it is dispensable for primitive stages of blood cell development but essentially required for definitive hematopoiesis. Using a conditional knock-out strategy, recent studies have indicated that c-myb is required for self-renewal of mouse hematopoietic stem cells. Here, we describe and characterize the c-myb mutant in a lower vertebrate, the zebrafish Danio rerio. The recessive loss-of-function allele of c-myb (c-myb(t25127)) was identified in a collection of N-ethyl-N-nitrosourea (ENU)-induced mutants exhibiting a failure of thymopoiesis. The sequence of the mutant allele predicts a missense mutation (I181N) in the middle of the DNA recognition helix of repeat 3 of the highly conserved DNA binding domain. In keeping with the findings in the mouse, primitive hematopoiesis is not affected in the c-myb mutant fish. By contrast, definitive hematopoiesis fails, resulting in the loss of all blood cells by day 20 of development. Thus, the mutant fish lack lymphocytes and other white and red blood cells; nonetheless, they survive for 2-3 mo but show stunted growth. Because the mutant fish survive into early adulthood, it was possible to directly show that their definitive hematopoiesis is permanently extinguished. Our results, therefore, suggest that the key role of c-myb in definitive hematopoiesis is similar to that in mammals and must have become established early in vertebrate evolution.
authors.affiliation: Department of Developmental Immunology, Max-Planck Institute of Immunobiology, D-79108 Freiburg, Germany.
authors.forename: Cristian
authors.initials: C
authors.lastname: Soza-Ried
authors.forename: Isabell
authors.initials: I
authors.lastname: Hess
authors.forename: Nikolai
authors.initials: N
authors.lastname: Netuschil
authors.forename: Michael
authors.initials: M
authors.lastname: Schorpp
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000502:physiology; D015027:Zebrafish / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology
chemical_list: D020598:Proto-Oncogene Proteins c-myb
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