Effect of Tbx1 knock-down on cardiac performance in zebrafish.
BACKGROUND
Tbx1 is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbx1(-/-) animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbx1 knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbx1 morpholino injected zebrafish embryos.


METHODS
To elucidate these issues, Tbx1 specific morpholino was used to reduce the function of Tbx1 in zebrafish. The differentiation of the myocardial cells was observed using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf). The cardiac performance was analyzed by measuring ventricular shortening fraction and atrial shortening fraction.


RESULTS
Tbx1 morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbx1 knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbx1 morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbx1 morpholino injected embryos.


CONCLUSIONS
Tbx1 might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbx1 knock down in zebrafish.
Zhang
Li-feng
LF
Children's Hospital, Fudan University, Shanghai 200032, China.
Gui
Yong-hao
YH
Wang
Yue-xiang
YX
Jiang
Qiu
Q
Song
Hou-yan
HY
D000818:Animals; D001934:Branchial Region / Q000166:cytology / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D017403:In Situ Hybridization; D009206:Myocardium / Q000166:cytology; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins