Fibronectin and integrin alpha 5 play requisite roles in cardiac morphogenesis

Mittal, Ashok; Pulina, Maria V.; Hou, Shuan-Yu; Astrof, Sophie

doi:10.1016/j.ydbio.2013.06.010

Cited by 65 publications

(65 citation statements)

References 41 publications

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“…Previous studies demonstrated that integrin α5β1 is a major Fn1 receptor in early and mid-gestation mouse embryos (Chen et al, 2015;George et al, 1997George et al, , 1993Mittal et al, 2013Mittal et al, , 2010Pulina et al, 2014Pulina et al, , 2011Takahashi et al, 2007;Yang et al, 1999Yang et al, , 1993. Therefore, we used conditional mutagenesis to ablate integrin α5 in the NC.…”

Section: Role Of Fn1 and Integrin α5 In Nc Development And Cardiovascmentioning

confidence: 99%

“…NC cells are known to express a number of Fn1 receptors, including αv-, α4-and α5-containing integrin heterodimers (Grazioli et al, 2006;Haack and Hynes, 2001;Testaz et al, 1999). Integrin α5β1 is thought to be a major Fn1 signal transducer during early to mid-gestation (George et al, 1997(George et al, , 1993Mittal et al, 2013Mittal et al, , 2010Pulina et al, 2014Pulina et al, , 2011Takahashi et al, 2007;Yang et al, 1999Yang et al, , 1993. Therefore, we asked whether integrin α5β1 was required for activation of Notch and differentiation of NC-derived cells into VSMCs.…”

Section: Fn1 Regulates Activation Of Notch and Nc Differentiation Intmentioning

confidence: 99%

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Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Wang

Astrof

2015

Development

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The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin α5β1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling.

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Section: Role Of Fn1 and Integrin α5 In Nc Development And Cardiovascmentioning

confidence: 99%

Section: Fn1 Regulates Activation Of Notch and Nc Differentiation Intmentioning

confidence: 99%

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Wang

Astrof

2015

Development

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“…In fact, ␣5␤1 FN interactions have been shown to be crucial for maintenance of mesodermal derivatives during postgastrulation stages and also for the survival of some NCCs (20). Integrin ␣5␤1 null embryos have cranial neural crest and endodermal cell death, which were shown to occur along their migration pathways (27). Although FN and FGF8 interaction has never been reported, binding of FN to its receptor ␣5␤1 has been shown to regulate FGF8 signaling in the pharyngeal arch region (27).…”

Section: Fibulin-1 Binds To Fgf8 and Their Effect On Embryo Developmentmentioning

confidence: 99%

“…Integrin ␣5␤1 null embryos have cranial neural crest and endodermal cell death, which were shown to occur along their migration pathways (27). Although FN and FGF8 interaction has never been reported, binding of FN to its receptor ␣5␤1 has been shown to regulate FGF8 signaling in the pharyngeal arch region (27). Because FBLN1 is a major binding partner of FN (28), it is possible that the FBLN1 effects on NCC migration might be regulated through partnership with FN along the migration paths from the hindbrain.…”

Section: Fibulin-1 Binds To Fgf8 and Their Effect On Embryo Developmentmentioning

confidence: 99%

Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity

Fresco

Kern

Mohammadi

et al. 2016

Journal of Biological Chemistry

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Fibulin-1 (FBLN1) is a member of a growing family of extracellular matrix glycoproteins that includes eight members and is involved in cellular functions such as adhesion, migration, and differentiation. FBLN1 has also been implicated in embryonic heart and valve development and in the formation of neural crestderived structures, including aortic arch, thymus, and cranial nerves. Fibroblast growth factor 8 (FGF8) is a member of a large family of growth factors, and its functions include neural crest cell (NCC) maintenance, specifically NCC migration as well as patterning of structures formed from NCC such as outflow tract and cranial nerves. In this report, we sought to investigate whether FBLN1 and FGF8 have cooperative roles in vivo given their influence on the development of the same NCC-derived structures. Surface plasmon resonance binding data showed that FBLN1 binds tightly to FGF8 and prevents its enzymatic degradation by ADAM17.

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“…Integrin-α5 KO mice die at E10.5 with severe vascular defects (Yang et al, 1993;Francis et al, 2002;Mittal et al, 2013), whereas genetic ablation of all five αv integrins leads to placental defects and haemorrhaging within the brain (Bader et al, 1998). Endothelium-specific deletion of both α5 and αv subunits, however, fails to replicate the angiogenic defects observed in global KO-mice, but instead leads to defects in the remodelling of the heart and great vessels (van der Flier et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo

et al. 2015

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The RGD-binding α5 and αv integrins have been shown to be key regulators of vascular smooth muscle cell (vSMC) function in vitro. However, their role on vSMCs during vascular development in vivo remains unclear. To address this issue, we have generated mice that lack α5, αv or both α5 and αv integrins on their vSMCs, using the SM22α-Cre transgenic mouse line. To our surprise, neither α5 nor αv mutants displayed any obvious vascular defects during embryonic development. By contrast, mice lacking both α5 and αv integrins developed interrupted aortic arches, large brachiocephalic/ carotid artery aneurysms and cardiac septation defects, but developed extensive and apparently normal vasculature in the skin. Cardiovascular defects were also found, along with cleft palates and ectopically located thymi, in Wnt1-Cre α5/αv mutants, suggesting that α5 and αv cooperate on neural crest-derived cells to control the remodelling of the pharyngeal arches and the septation of the heart and outflow tract. Analysis of cultured α5/αv-deficient vSMCs suggests that this is achieved, at least in part, through proper assembly of RGD-containing extracellular matrix proteins and the correct incorporation and activation of latent TGF-β.

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Fibronectin and integrin alpha 5 play requisite roles in cardiac morphogenesis

Cited by 65 publications

References 41 publications

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity

α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo

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