Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2.
The establishment of chamber specificity is an essential requirement for cardiac morphogenesis and function. Hesr1 (Hey1) and Hesr2 (Hey2) are specifically expressed in the atrium and ventricle, respectively, implicating these genes in chamber specification. In our current study, we show that the forced expression of Hesr1 or Hesr2 in the entire cardiac lineage of the mouse results in the reduction or loss of the atrioventricular (AV) canal. In the Hesr1-misexpressing heart, the boundaries of the AV canal are poorly defined, and the expression levels of specific markers of the AV myocardium, Bmp2 and Tbx2, are either very weak or undetectable. More potent effects were observed in Hesr2-misexpressing embryos, in which the AV canal appears to be absent entirely. These data suggest that Hesr1 and Hesr2 may prevent cells from expressing the AV canal-specific genes that lead to the precise formation of the AV boundary. Our findings suggest that Tbx2 expression might be directly suppressed by Hesr1 and Hesr2. Furthermore, we find that the expression of Hesr1 and Hesr2 is independent of Notch2 signaling. Taken together, our data demonstrate that Hesr1 and Hesr2 play crucial roles in AV boundary formation through the suppression of Tbx2.
Kokubo
Hiroki
H
Division of Mammalian Development, National Institute of Genetics, 1111 Yata, Mishima Shizuoka 411-8540, Japan. hkokubo@lab.nig.ac.jp
Tomita-Miyagawa
Sachiko
S
Hamada
Yoshio
Y
Saga
Yumiko
Y
D000818:Animals; D001283:Atrioventricular Node / Q000196:embryology / Q000254:growth & development*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D038081:Organogenesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C120420:Hey1 protein, mouse; C485778:Hey2 protein, mouse; C097348:T-Box Domain Protein 2