An acyltransferase controls the generation of hematopoietic and endothelial lineages in zebrafish.
Hematopoietic and endothelial cells develop from a common progenitor, the hemangioblast, or directly from mesodermal cells. The molecular pathway that regulates the specification of both cell lineages remains elusive. Here, we show that a lysocardiolipin acyltransferase, lycat, is critical for the establishment of both hematopoietic and endothelial lineages. We isolated lycat from the deletion interval of cloche, a zebrafish mutant that has dramatically reduced hematopoietic and endothelial cell lineages. Reduction of lycat mRNA levels in wild-type zebrafish embryos decreases both endothelial and hematopoietic lineages. Lycat mRNA rescues blood lineages in zebrafish cloche mutant embryos. E165R and G166L mutations in the highly conserved catalytic domain in lycat abolish its function in zebrafish hematopoiesis. Epistasis analysis supports that lycat acts upstream of scl and etsrp in zebrafish hemangioblast development. These data indicate that lycat is the earliest known player in the generation of both endothelial and hematopoietic lineages.
Xiong
Jing-Wei
JW
The Nephrology Division, Massachusetts General Hospital-East, Harvard Medical School, 149 13th St, Room 8216, Charlestown, MA 02129, USA. Xiong@cvrc.mgh.harvard.edu
Yu
Qingming
Q
Zhang
Jiaojiao
J
Mably
John D
JD
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000201:enzymology*; D042783:Endothelial Cells / Q000201:enzymology*; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D051379:Mice; D009025:Morpholines / Q000378:metabolism; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D000217:Acyltransferases; D051792:Basic Helix-Loop-Helix Proteins; D009025:Morpholines; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D029961:Zebrafish Proteins; C509408:Etv2 protein, zebrafish; C489367:tal1 protein, zebrafish; C525544:lysocardiolipin acyltransferase, mouse