Corrigendum to “Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus” [Dev. Biol. 279 (2005) 179–192]

Garriock, Robert J.; D'Agostino, Susan L.; Pilcher, Karen C.; Krieg, Paul A.

doi:10.1016/j.ydbio.2008.07.013

Cited by 1 publication

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“…4). On the other hand, embryos with the reduced wnt11-Related gene (wnt11-R) expression exhibited cardia bifida, but not the inhibition of cardiac differentiation (48). In that study, aberrant contact within the myocardial wall leads to defects in fusion of the heart tube.…”

Section: Discussionmentioning

confidence: 83%

HIF-1α Signaling Upstream of NKX2.5 Is Required for Cardiac Development in Xenopus

Nagao

Taniyama

Kietzmann

et al. 2008

Journal of Biological Chemistry

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HIF-1␣ is originally identified as a transcription factor that activates gene expression in response to hypoxia. In metazoans, HIF-1␣ functions as a master regulator of oxygen homeostasis and regulates adaptive responses to change in oxygen tension during embryogenesis, tissue ischemia, and tumorigenesis. Because Hif-1␣-deficient mice exhibit a number of developmental defects, the precise role of HIF-1␣ in early cardiac morphogenesis has been uncertain. Therefore, to clarify the role of HIF-1␣ in heart development, we investigated the effect of knockdown of HIF-1␣ in Xenopus embryos using antisense morpholino oligonucleotide microinjection techniques. Knockdown of HIF-1␣ resulted in defects of cardiogenesis. Whole mount in situ hybridization for cardiac troponin I (cTnI) showed the two separated populations of cardiomyocytes, which is indicative of cardia bifida, in HIF-1␣-depleted embryos. Furthermore, the depletion of HIF-1␣ led to the reduction in cTnI expression, suggesting the correlation between HIF-1␣ and cardiac differentiation. We further examined the expression of several heart markers, nkx2.5, gata4, tbx5, bmp4, hand1, and hand2 in HIF-1␣-depleted embryos. Among them, the expression of nkx2.5 was significantly reduced. Luciferase reporter assay using the Nkx2.5 promoter showed that knockdown of HIF-1␣ decreased its promoter activity. The cardiac abnormality in the HIF-1␣-depleted embryo was restored with co-injection of nkx2.5 mRNA. Collectively, these findings reveal that HIF-1␣-regulated nkx2.5 expression is required for heart development in Xenopus. Hypoxia inducible factor-1 (HIF-1)2 is a transcriptional factor that has the fundamental function in mammalian development and homeostasis, and is considered to become a target for therapy in cancer and cardiac ischemia (1). In response to localized tissue hypoxia, HIF-1 is activated to regulate the transcription of hypoxia-inducible genes that mediate angiogenesis, erythropoiesis, vasodilation, and anaerobic metabolism (2). Under normoxic conditions, the ␣ subunit of HIF-1 (HIF-1␣) undergoes rapid decay via a ubiqutin-proteasome degradation pathway involving the von Hippel-Lindau tumor suppressor gene product (pVHL) (3-5). Hypoxia prevents ␣ subunit from ubiquitination, thereby allowing HIF-1␣ to escape from proteolysis, to dimerize with constitutively expressed HIF-1␤ (6), and to translocate into the nucleus with HIF-1␤.In the early development of mammals, the natural progression of organogenesis involves hypoxia. Diffusion of oxygen in the embryo is limited by its size shortly after gastrulation. In turn, molecular responses to oxygen gradients by HIF-1 are responsible for proper differentiation and maintenance of the cardiovascular system (7). Null mutation of either Hif-1␣ or Hif-1␤ in mice leads to midgestational lethality of embryos, accompanied with phenotypes that include defects in the vasculature, placenta, and heart at embryonic day 10.5 (E10.5) (2, 8, 9). Thus, improper response to low oxygen in the embryo leads to abnormal cardiovascular m...

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Section: Discussionmentioning

confidence: 83%