Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFβ receptor (Tgfbr2) mutant mice

Choudhary, Bibha; Ito, Yoshihiro; Makita, Takako; Sasaki, Taro; Chai, Yang; Sucov, Henry M.

doi:10.1016/j.ydbio.2005.11.008

Cited by 86 publications

(120 citation statements)

References 23 publications

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“…Early during embryonic development, TGF-b signaling is required for formation of the vascular plexus and differentiation of both endothelial cells and VSMCs (Dickson et al 1995;Oshima et al 1996; Goumans and Mummery 2000; Larsson et al 2001;Carvalho et al 2007;Goumans et al 2009). TGF-b signaling is also required for morphogenesis of the cardiac outflow tract and VSMC-dependent deposition of elastic fibers (Wurdak et al 2005;Choudhary et al 2006).…”

Section: Tgf-b Signaling In Vascular Homeostasismentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

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Section: Tgf-b Signaling In Vascular Homeostasismentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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“…101,102 Targeted deletion of Tgfbr1 or Tgfbr2 in neural crest cells leads to OFT defects (PTA, interrupted aortic arch and ventricular septal defect [VSD]), strongly suggesting that TGFβ signaling is necessary for cardiac neural crest cells to promote normal septation of the OFT. [101][102][103] Other mouse models with targeted deletions in BMP/TGFβ signaling Overview on developmental stages of the heart. The cardiac crescent is formed around day 15 in humans.…”

Section: Heart Development Is Coordinated By Multiple Signaling Networkmentioning

confidence: 99%

Cilia and coordination of signaling networks during heart development

et al. 2013

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“…Furthermore, the Cx43-null mutant phenotype, characterized by infundibular bulging without septation defects, differs from other murine genetic models that affect CNC function. Genetic models including those with mutations in or knockouts of Pax3, neurotrophin 3/TrkC, TGF␤ receptor type II, BMP4, BMP receptor IA, endothelin 1 and combinations of retinoic acid receptors (Choudhary et al, 2006;Donovan et al, 1996;Epstein et al, 2000;Kurihara et al, 1995;Liu et al, 2004;Mendelsohn et al, 1994;Stottmann et al, 2004;Youn et al, 2003) commonly cause OFT septation defects similar to those resulting from chick NC ablation. Thus, during development, Cx43 may be required in tissues that contribute to heart formation other than or in addition to the CNC (Li et al, 2002;Walker et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

Liu

Schneider

et al. 2006

Development

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Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior studies suggest a vital role for CNC expression of Cx43 in heart development. Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT phenotype, although coronary vasculature was abnormal in this mutant line. A broader CKO mediated by P3pro (Pax3)-Cre, involving both ventral and dorsal aspects of the thoracic neural tube and CNC, resulted in infundibular bulging and coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre-mediated loss of Cx43 in the neural tube was characterized by a late phase of cellular delamination from the dorsal and lateral neural tube, a markedly increased abundance of neuroepithelium-derived cells outside of the neural tube and an excess of such cells infiltrating the heart and infundibulum. Thus, expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43 is not required in the CNC for normal OFT morphogenesis. Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development.

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Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFβ receptor (Tgfbr2) mutant mice

Cited by 86 publications

References 23 publications

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Cilia and coordination of signaling networks during heart development

Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube

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