2014
DOI: 10.1016/j.ydbio.2014.09.031
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Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

Abstract: Recent studies using mouse models for cell fate tracing of epicardial derived cells (EPDCs) have demonstrated that at the atrioventricular (AV) junction EPDCs contribute to the mesenchyme of the AV sulcus, the annulus fibrosus, and the parietal leaflets of the AV valves. There is little insight, however, into the mechanisms that govern the contribution of EPDCs to these tissues. While it has been demonstrated that bone morphogenetic protein (Bmp) signaling is required for AV cushion formation, its role in regu… Show more

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Cited by 25 publications
(34 citation statements)
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References 37 publications
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“…Therefore, the requirements for Bmpr1a in PostnCre lineage cells, present in embryonic and adult valves after endocardial cushion formation, were examined. Although BMP signaling plays essential roles during endocardial cushion EndMT 24, 26 , PostnCre;Bmpr1a flox/flox mice are viable and the hearts are grossly normal at postnatal day (P)1, similar to Bmpr1a flox/flox control mice (Supplementary Figure V). In addition, Pentachrome staining demonstrates normal heart morphology, in addition to normal heart valve stratification and ECM composition of PostnCre;Bmpr1a flox/flox aortic and mitral valves (Supplementary Figure V), when compared to control P1 hearts.…”
Section: Resultsmentioning
confidence: 98%
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“…Therefore, the requirements for Bmpr1a in PostnCre lineage cells, present in embryonic and adult valves after endocardial cushion formation, were examined. Although BMP signaling plays essential roles during endocardial cushion EndMT 24, 26 , PostnCre;Bmpr1a flox/flox mice are viable and the hearts are grossly normal at postnatal day (P)1, similar to Bmpr1a flox/flox control mice (Supplementary Figure V). In addition, Pentachrome staining demonstrates normal heart morphology, in addition to normal heart valve stratification and ECM composition of PostnCre;Bmpr1a flox/flox aortic and mitral valves (Supplementary Figure V), when compared to control P1 hearts.…”
Section: Resultsmentioning
confidence: 98%
“…PostnCre 22 is active in aortic VICs, but not in endothelial cells, and is expressed robustly throughout the AoV 23 . The BMP Type IA receptor ALK3 ( Bmpr1a ) is required for BMP-mediated phosphorylation of Smad1/5/8 in many tissues, including heart valve progenitors 24 . Tie2Cre and Wnt1Cre are active in a subset of aortic VICs, and deletion of Bmpr1a in either of these lineages causes embryonic lethality 25, 26 .…”
Section: Resultsmentioning
confidence: 99%
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“…In addition, the deposition of cardiac jelly at the onset of AV valve formation physically separates the AVC myocardium from the endocardium, preventing Cx40-inducing endocardial-derived cues from reaching AVC myocytes . From approximately E12 onwards, epicardial mesenchyme penetrates the myocardium between the AVC and ventricular myocardium and contacts the endocardium-derived cushion/valve mesenchyme to form the annulus fibrosus (Wessels et al, 1996;Zhou et al, 2010;Lockhart et al, 2014), thus insulating the atrial and ventricular working myocardium. Tbx3 + cells of the AVC form the definitive AVN and AV ring bundles at the atrial side of the annulus fibrosus.…”
Section: The Origin and Development Of The Avc And Avnmentioning
confidence: 99%
“…These additional sites of recombination should be considered especially when investigating embryonic deletion strategies as alterations in the valves can also lead to cardiac phenotypes [73]. …”
Section: Tissue Resident Fibroblastsmentioning
confidence: 99%