BMP signaling is required for septation of the outflow tract of the mammalian heart

Délot, Emmanuèle C.; Bahamonde, Matthew E.; Zhao, Manxu; Lyons, Karen M.

doi:10.1242/dev.00181

Cited by 191 publications

(144 citation statements)

References 61 publications

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“…This notion of distinct, dosage-dependent functions for Bmp signaling likely also applies to the SHF and SHF derivatives as suggested by the OFT phenotype of the Bmpr2 hypomorph previously reported by Lyons and colleagues (46). Moreover, we have recently found that Bmp2 and Bmp4 function cooperatively in the SHF to regulate distinct events in the forming OFT (L. Ma and J.F.M., unpublished observations).…”

Section: Wnt Signaling Is Critical For Development Of the Right Ventrsupporting

confidence: 70%

Canonical Wnt signaling functions in second heart field to promote right ventricular growth

Wang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

179

138

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The second heart field (SHF), progenitor cells that are initially sequestered outside the heart, migrates into the heart and gives rise to endocardium, myocardium, and smooth muscle. Because of its distinct developmental history, the SHF is likely subjected to different signals from that of the first heart field. Previous experiments revealed that canonical Wnt signaling negatively regulated first heart field specification. We inactivated the obligate canonical Wnt effector ␤-catenin using a ␤-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of ␤-catenin to model continuous Wnt signaling in SHF. Our data indicate that Wnt signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgf␤2 expression was drastically reduced in ␤-catenin loss-of-function mutants, indicating that Wnt signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium.conditional genetics ͉ cardiac progenitor ͉ mouse ͉ development

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Section: Wnt Signaling Is Critical For Development Of the Right Ventrsupporting

confidence: 70%

Canonical Wnt signaling functions in second heart field to promote right ventricular growth

Wang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

179

138

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“…A homozygous mouse defective for BMPR-II receptormediated signaling revealed outflow tract defects, including the absence of septation of the conotruncus below the valve level. 24 Further investigation of the BMP pathway in mouse cardiac development demonstrated that ablation of the BMP type I receptor ALK-3 in neural crest cells also leads to severe outflow tract defects, including failure of septation. 25 Taken together, these data raise the intriguing possibility that BMPR2 mutations may lead to congenital heart defects in humans and may be a predisposition to PAH.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Receptor Mutations and Pulmonary Arterial Hypertension in Childhood

Berger²,

et al. 2005

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Background-Pulmonary arterial hypertension (PAH) is a potentially fatal vasculopathy that can develop at any age.Adult-onset disease has previously been associated with mutations in BMPR2 and ALK-1. Presentation in early life may be associated with congenital heart disease but frequently is idiopathic. Methods and Results-We performed mutation analysis in genes encoding receptor members of the transforming growth factor-␤ cell-signaling pathway in 18 children (age at presentation Ͻ6 years) with PAH. Sixteen children were initially diagnosed with idiopathic PAH and 2 with PAH in association with congenital heart defects. Germ-line mutations were observed in 4 patients (22%) (age at disease onset, 1 month to 6 years), all of whom presented with idiopathic PAH. The BMPR2 mutations (nϭ2, 11%) included a partial gene deletion and a nonsense mutation, both arising de novo in the proband. Importantly, a missense mutation of ALK-1 and a branch-site mutation of endoglin were also detected. Presenting clinical features or progression of pulmonary hypertension did not distinguish between patients with mutations in the different genes or between those without mutations. Conclusions-The

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“…BMP and FGF signaling pathways have previously been shown to be important for normal heart development including endocardial cushion formation, cushion elongation, and remodeling (Galvin et al, 2000;Gaussin et al, 2002;Delot et al, 2003;Jiao et al, 2003;Sugi et al, 2003Sugi et al, , 2004Somi et al, 2004;Ma et al, 2005;Lincoln et al, 2006a). A number of BMP ligands have been identified in the developing heart; in particular, BMP4 is expressed in the OFT myocardium adjacent to the endocardial cushions during early stages of valve development (Keyes et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

BMP and FGF regulatory pathways in semilunar valve precursor cells

Zhao

Etter

Hinton

et al. 2007

Developmental Dynamics

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BMP signaling is required for septation of the outflow tract of the mammalian heart

Abstract: SUMMARY DEVELOPMENT AND DISEASE BMP signaling is required for septation of the outflow tract of the mammalian heart

Cited by 191 publications

References 61 publications

Canonical Wnt signaling functions in second heart field to promote right ventricular growth

Canonical Wnt signaling functions in second heart field to promote right ventricular growth

Transforming Growth Factor-β Receptor Mutations and Pulmonary Arterial Hypertension in Childhood

BMP and FGF regulatory pathways in semilunar valve precursor cells

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