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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4178-4184
HEMATOPOIESIS
Zebrafish homolog of the leukemia gene CBFB: its
expression during embryogenesis and its relationship to scl
and gata-1 in hematopoiesis
Trevor Blake,
Neeraj Adya,
Cheol-Hee Kim,
Andrew C. Oates,
Leonard Zon,
Ajay Chitnis,
Brant M. Weinstein, and
P. Paul Liu
From the National Human Genome Research Institute,
National Institutes of Health, Bethesda, MD; Howard Hughes Medical
Institute, Children's Hospital, Boston, MA; and National Institute of
Child Health and Human Development, National Institutes of Health,
Bethesda, MD.
Mammalian CBFB encodes a transcription factor (CBF )
that in combination with CBF 2 binds to specific DNA sequences and
regulates expression of a number of hematopoietic genes.
CBFB is associated with human leukemias through a
chromosome 16 inversion and is essential for definitive hematopoiesis
during mouse embryo development. We have isolated a zebrafish
cbfb complementary DNA (cDNA) clone from a zebrafish kidney cDNA
library. This cbfb is highly homologous to human and mouse
CBFB/Cbfb genes at both the DNA and protein level. In
biochemical analyses, cbf binds to human CBF2 and enhances its
DNA binding. During zebrafish development, cbfb is expressed in the lateral plate mesoderm at tail bud stage and in the
intermediate cell mass (ICM, the location of embryonic hematopoiesis)
between the 21- to 26-somite stages. The cbfb is also
expressed in Rohon-Beard cells, cranial nerve ganglia, hindbrain, retina, branchial arches, jaw, and fin buds. Expression of
cbfb is decreased or absent in the ICM and
Rohon-Beard cells in some hematopoietic mutants and is unaffected in
others. We have also analyzed the expression of scl and
gata-1 in the same hematopoietic mutants to ascertain the
relative order of these transcription factors to cbfb in
zebrafish hematopoiesis. Our results indicate that cbfb is
expressed in early hematopoietic progenitors and that its expression
pattern in the hematopoietic mutants is similar to that of
scl.
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