Glycogen synthase kinase 3 ß modulates cardiogenesis in zebrafish
Date Issued
2005
Date
2005
Author(s)
Liao, Pei-Yin
DOI
en-US
Abstract
Glycogen synthase kinase 3β (GSK3β) encodes a multifunctional serine/threonine protein kinase, which is ubiquitously expressed in organisms. Although GSK3β is known to play roles in many biological processes, including cell survival, tumorigenesis and developmental patterning, it remains unclear that the function of GSK3β in cardiogenesis in vivo. We used a GFP-tagged heart transgenic zebrafish to address this question. In order to specifically inhibit GSK3β, gsk3β antisense morpholino oligonucleotide (gsk3β-MO) was injected into one-celled embryos to block the translation of the gsk3β mRNA. In gsk3β-MO -injected embryos, we found that heart precursor cells lined up at the midline at 24 hpf, failed to complete the heart positioning, and then stretched slowly to a thin, ‘string-like’ shape about 96 hpf. In addition, in this morphants, the heart rate was slower, the contraction was weaker, and pericardial edema was commonly observed. Knowdown of GSK3β resulted in a severe disruption of early (jogging) and late (looping) aspects of cardiac left-right asymmetry. The degree of cardiac defects due to GSK3β attenuation was dose-dependent. But these defectives could be rescued by injecting synthetic gsk3β mRNA. Consistent with the morphological change of heart, the expression of bmp4, a heart-asymmetry marker and a target of Wnt/β-catenin signaling pathway, was upregulated in GSK3β morphants: the asymmetry of heart was completely disrupted. Interestingly, we found that cardiac defects happened in the gsk3β-MO-injected embryos were similar to those observed in axin1 morphants. Therefore, our findings strongly suggest that GSK3β plays a role in L/R-biased heart positioning through Wnt/β-catenin pathway during zebrafish cardiogenesis.
Subjects
斑馬魚
心臟發育
肝醣生成酵素激酶
zebrafish
cardiogenesis
GSK
Type
other
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