TBX1, a DiGeorge syndrome candidate gene, is inhibited by retinoic acid.
Both retinoic acid (RA) and Tbx1 are definitively indispensable for the development of the pharyngeal arches. The defects produced by a loss of Tbx1 highly resemble those induced by hyper- and hypo-RA. Based on these similarities, the effects of RA on Tbx1 expression pattern were explored during pharyngeal arch development in zebrafish. Whole-mount in situ hybridization and real-time quantitative PCR were used. Zebrafish embryos were treated with 5 x 10(-8)mol/L and 10(-7)mol/L RA at 12.5 hours post fertilization for 1.5 hours, respectively. Whole-mount in situ hybridization showed that Tbx1 was expressed in the cardiac region, pharyngeal arch and otic vesicle between 24 hpf and 72 hpf in zebrafish. Tbx1 expression was obviously reduced, even lost, in the pharyngeal arch and outflow tract in RA treated groups. Real-time quantitative PCR analysis showed that Tbx1 expression rose to a peak level at 36 hpf in wild type group. Repression of Tbx1 expression was most evident at 36 hpf, 24 hours after RA treatment. 10(-7 )mol/L RA caused a more severe effect on the Tbx1 expression level than 5 x 10(-8)mol/L RA. The results suggested that RA could produce an altered Tbx1 expression pattern in zebrafish. In addition, RA could repress Tbx1 expression in a dose-dependent manner.
Zhang
Lifeng
L
Children's Hospital of Fudan University, Shanghai, P.R. China.
Zhong
Tao
T
Wang
Yuexiang
Y
Jiang
Qiu
Q
Song
Houyan
H
Gui
Yonghao
Y
D000818:Animals; D001934:Branchial Region / Q000187:drug effects / Q000196:embryology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*
D004268:DNA-Binding Proteins; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D029961:Zebrafish Proteins; C119156:tbr1b protein, zebrafish; D014212:Tretinoin