The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis.
In vertebrates, hematopoietic and vascular progenitors develop from ventral mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood cells, whereas progenitor cells of subsequent definitive waves form all hematopoietic cell lineages. In this report we examine the development of hematopoietic and vasculogenic cells in normal zebrafish and characterize defects in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study. Expression of these genes identifies embryonic regions that contain hematopoietic and vascular progenitor cells. The expression of c-myb also identifies definitive hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is not required for primitive erythropoiesis in zebrafish even though it is expressed in these cells. Both cloche and spadetail mutant embryos have defects in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs.
Thompson
M A
MA
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Ransom
D G
DG
Pratt
S J
SJ
MacLennan
H
H
Kieran
M W
MW
Detrich
H W
HW
Vail
B
B
Huber
T L
TL
Paw
B
B
Brownlie
A J
AJ
Oates
A C
AC
Fritz
A
A
Gates
M A
MA
Amores
A
A
Bahary
N
N
Talbot
W S
WS
Her
H
H
Beier
D R
DR
Postlethwait
J H
JH
Zon
L I
LI
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513186:lmo2 protein, zebrafish