Patent ductus arteriosus in mice with smooth muscle-specific <i>Jag1</i> deletion

Feng, Xuesong; Krebs, Luke T.; Gridley, Thomas

doi:10.1242/dev.052043

Cited by 78 publications

(97 citation statements)

References 44 publications

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“…In recent work, expression of contractile smooth muscle marker genes was found to be down-regulated in the ductus arteriosus of Jagged1 flox/flox Sma22-Cre embryos (21). Interestingly, we also observed down-regulation of contractile smooth muscle marker genes in the absence of VSMC-derived Jagged1 (supplemental Fig.…”

Section: Abnormal Pulmonary Artery Morphology and Smooth Muscle Markesupporting

confidence: 68%

“…All TaqMan probes were obtained from Applied Biosystems. For contractile smooth muscle-related genes, qPCR was performed with fast SYBR reagent (Invitrogen) as described (21). GAPDH was used as an internal control.…”

Section: Methodsmentioning

confidence: 99%

“…1A). To determine whether these morphological abnormalities are associated with changes in expression of smooth musclerelated genes in the Notch3 Ϫ/Ϫ mouse, we quantified mRNAs for transgelin (Sma22), ␣-SMA, ␥-SMA, smoothelin, and calponin as described (21). At all ages examined, downregulation of these genes was observed in Notch3 Ϫ/Ϫ mice (Fig.…”

Section: Abnormal Pulmonary Artery Morphology and Smooth Muscle Markementioning

confidence: 99%

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Activation Dynamics and Signaling Properties of Notch3 Receptor in the Developing Pulmonary Artery

Ghosh

Paez-Cortez

Boppidi

et al. 2011

Journal of Biological Chemistry

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Notch3 signaling is fundamental for arterial specification of systemic vascular smooth muscle cells (VSMCs). However, the developmental role and signaling properties of the Notch3 receptor in the mouse pulmonary artery remain unknown. Here, we demonstrate that Notch3 is expressed selectively in pulmonary artery VSMCs, is activated from late fetal to early postnatal life, and is required to maintain the morphological characteristics and smooth muscle gene expression profile of the pulmonary artery after birth. Using a conditional knock-out mouse model, we show that Notch3 receptor activation in VSMCs is Jagged1-dependent. In vitro VSMC lentivirus-mediated Jagged1 knockdown, confocal localization analysis, and co-culture experiments revealed that Notch3 activation is cell-autonomous and occurs through the physical engagement of Notch3 and VSMC-derived Jagged1 in the interior of the same cell. Although the current models of mammalian Notch signaling involve a two-cell system composed of a signal-receiving cell that expresses a Notch receptor on its surface and a neighboring signal-sending cell that provides membrane-bound activating ligand, our data suggest that pulmonary artery VSMC Notch3 activation is cell-autonomous. This unique mechanism of Notch activation may play an important role in the maturation of the pulmonary artery during the transition to air breathing.Lung development involves the integration of multiple signaling pathways to ensure coordinated growth and differentiation of airway and vascular structures (1). The initial event in vessel development is the formation of basic tubular structures from endothelial precursors (2). Under the influence of PDGF-␤ and Wnt signaling (3, 4), formation of mature vessels occurs by the stepwise recruitment, growth, and differentiation of mesenchymal precursors into a circumferential mural cell layer composed of smooth muscle cells and pericytes (5).It is noteworthy that the lung vascular system is subjected to a dramatic switch at birth, from a low-flow, low-pressure fetal state to a high-flow, higher pressure postnatal state (1). Although it recognized as an essential feature of the transition from intrauterine life, the timing and identification of signals that control how lung vascular cells adapt to this changeover remain unclear. The involvement of Notch signals in multiple aspects of vessel development led us to investigate the role of this pathway during this transition period.The Notch signaling pathway is highly conserved across species, controlling cell fate decisions and tissue patterning during development (6). In classical Notch signaling, a cell surface Notch receptor is activated by binding with a membranebound ligand delivered by a neighboring signal-sending cell (7). This interaction initiates a series of proteolytic cleavages that release the Notch intracellular domain into the cytoplasm of the signal-receiving cell before translocation to the nucleus and induction of target gene transcription (8, 9).Of the four mammalian Notch receptors, Notch3...

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Section: Abnormal Pulmonary Artery Morphology and Smooth Muscle Markesupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Abnormal Pulmonary Artery Morphology and Smooth Muscle Markementioning

confidence: 99%

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Activation Dynamics and Signaling Properties of Notch3 Receptor in the Developing Pulmonary Artery

Ghosh

Paez-Cortez

Boppidi

et al. 2011

Journal of Biological Chemistry

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“…In Tbx18-Cre:RBPJk flox/flox mice, specification of coronary arterial endothelial fate is unaffected, but CoSMC differentiation is impaired. 23 Notch has been shown to regulate SMC differentiation in the systemic vasculature, 123,124 suggesting that this might be a general role for Notch. Notch regulates SMC differentiation through cooperation with TGF-␤1, 125 similar to the findings of Grieskamp et al 23 regarding CoSMC differentiation from EPDCs (Figures 2 and 5).…”

Section: Pérez-pomares and De La Pompamentioning

confidence: 99%

Signaling During Epicardium and Coronary Vessel Development

Pérez‐Pomares

Pompa

2011

Circulation Research

133

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Abstract:The epicardium, the tissue layer covering the cardiac muscle (myocardium), develops from the proepicardium, a mass of coelomic progenitors located at the venous pole of the embryonic heart. Proepicardium cells attach to and spread over the myocardium to form the primitive epicardial epithelium. The epicardium subsequently undergoes an epithelial-to-mesenchymal transition to give rise to a population of epicardiumderived cells, which in turn invade the heart and progressively differentiate into various cell types, including cells of coronary blood vessels and cardiac interstitial cells. Epicardial cells and epicardium-derived cells signal to the adjacent cardiac muscle in a paracrine fashion, promoting its proliferation and expansion. Recently, high expectations have been raised about the epicardium as a candidate source of cells for the repair of the damaged heart. Because of its developmental importance and therapeutic potential, current research on this topic focuses on the complex signals that control epicardial biology. This review describes the signaling pathways involved in the different stages of epicardial development and discusses the potential of epicardial signals as targets for the development of therapies to repair the diseased heart. (Circ Res. 2011;109:1429-1442.)

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“…Mice with SMC-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from PDA (Feng, 2010). These mice exhibit defects in contractile SMC differentiation in the medial vascular wall of the DA, which therefore fails to express contractile SMC proteins.…”

Section: Jag1mentioning

confidence: 99%