Identification of RNA binding motif proteins essential for cardiovascular development.
BACKGROUND
We recently identified Rbm24 as a novel gene expressed during mouse cardiac development. Due to its tightly restricted and persistent expression from formation of the cardiac crescent onwards and later in forming vasculature we posited it to be a key player in cardiogenesis with additional roles in vasculogenesis and angiogenesis.


RESULTS
To determine the role of this gene in cardiac development, we have identified its zebrafish orthologs (rbm24a and rbm24b), and functionally evaluated them during zebrafish embryogenesis. Consistent with our underlying hypothesis, reduction in expression of either ortholog through injection of morpholino antisense oligonucleotides results in cardiogenic defects including cardiac looping and reduced circulation, leading to increasing pericardial edema over time. Additionally, morphant embryos for either ortholog display incompletely overlapping defects in the forming vasculature of the dorsal aorta (DA), posterior caudal vein (PCV) and caudal vein (CV) which are the first blood vessels to form in the embryo. Vasculogenesis and early angiogenesis in the trunk were similarly compromised in rbm24 morphant embryos at 48 hours post fertilization (hpf). Subsequent vascular maintenance was impaired in both rbm24 morphants with substantial vessel degradation noted at 72 hpf.


CONCLUSIONS
Taken collectively, our functional data support the hypothesis that rbm24a and rbm24b are key developmental cardiac genes with unequal roles in cardiovascular formation.
Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Samantha
S
Maragh
Ronald A
RA
Miller
Seneca L
SL
Bessling
David M
DM
McGaughey
Marja W
MW
Wessels
Bianca
B
de Graaf
Eric A
EA
Stone
Aida M
AM
Bertoli-Avella
John D
JD
Gearhart
Shannon
S
Fisher
Andrew S
AS
McCallion
D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002319:Cardiovascular System / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009024:Morphogenesis / Q000235:genetics; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D016601:RNA-Binding Proteins; C572909:Rbm24a protein, zebrafish; C572910:Rbm24b protein, zebrafish; D029961:Zebrafish Proteins; D012313:RNA