Essential roles of fibronectin in the development of the left–right embryonic body plan

Pulina, Maria V.; Hou, Shuan-Yu; Mittal, Ashok; Jülich, Dörthe; Whittaker, Charlie; Holley, Scott A.; Hynes, Richard O.; Astrof, Sophie; Whittaker, Charles A.

doi:10.1016/j.ydbio.2011.05.178

Cited by 2 publications

(4 citation statements)

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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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“…ECM proteins have been implicated in morphogenesis of the organizer. Fibronectin participates in the development of embryonic L-R asymmetry, by controlling the organization of cells into a single layer in the mouse node, without affecting cilia length (Pulina et al, 2011). In zebrafish, integrin α5 is expressed in the dorsal forerunner cells and is required for the morphogenesis of a single intact KV (Ablooglu et al, 2010).…”

Section: Research Article Laminin and Organ Lateralitymentioning

confidence: 99%

“…For example, disruption of integrinα5β1 or fibronectin during gastrulation affects the development of the node/KV in zebrafish and Xenopus, resulting in defective L-R asymmetry (Ablooglu et al, 2010;Pulina et al, 2011). Studies in mouse and Xenopus have shown that proteoglycans facilitate and provide directional cues for rapid propagation of Nodal and Lefty signaling from the node to the left LPM (Oki et al, 2007), and subsequently from the left to the right LPM (Oki et al, 2007;Marjoram and Wright, 2011).…”

Section: Introductionmentioning

confidence: 99%

Laminin β1a controls distinct steps during the establishment of digestive organ laterality

et al. 2013

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SUMMARYVisceral organs, including the liver and pancreas, adopt asymmetric positions to ensure proper function. Yet the molecular and cellular mechanisms controlling organ laterality are not well understood. We identified a mutation affecting zebrafish laminin β1a (lamb1a) that disrupts left-right asymmetry of the liver and pancreas. In these mutants, the liver spans the midline and the ventral pancreatic bud remains split into bilateral structures. We show that lamb1a regulates asymmetric left-right gene expression in the lateral plate mesoderm (LPM). In particular, lamb1a functions in Kupffer's vesicle (KV), a ciliated organ analogous to the mouse node, to control the length and function of the KV cilia. Later during gut-looping stages, dynamic expression of Lamb1a is required for the bilayered organization and asymmetric migration of the LPM. Loss of Lamb1a function also results in aberrant protrusion of LPM cells into the gut. Collectively, our results provide cellular and molecular mechanisms by which extracellular matrix proteins regulate left-right organ morphogenesis. KEY WORDS: Asymmetry, Laminin, OrganogenesisLaminin β1a controls distinct steps during the establishment of digestive organ laterality Tatiana Here, we report that laminin plays an essential role in the establishment of L-R asymmetry of the zebrafish liver and pancreas. Laminins are large heterotrimeric glycoproteins, comprising of α, β and γ chains assembled into a cross-shaped molecule with a long arm and three short globular arms (Engel et al., 1981;Miner, 2008). We present a novel mutant allele of the laminin β1a (lamb1a) gene, which encodes a subunit of the ECM protein laminin 1. In this mutant, the liver spans the midline, and the ventral pancreatic bud remains split into bilateral structures. We find that laminin is necessary for controlling cilia length and fluid flow in the KV, and for restricting southpaw expression to the left LPM. Subsequently, lamb1a deficiency disrupts the dynamic deposition of laminin 1 in the LPM epithelium, resulting in a severely disorganized epithelium with abnormal protrusions into the gut, and a failure of asymmetric gut looping. Thus, laminin 1 participates in sequential events that are important for the establishment of L-R asymmetry of visceral organs, including an early role in the KV and a later role in the LPM.

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Essential roles of fibronectin in the development of the left–right embryonic body plan

Cited by 2 publications

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Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Neural crest cell-autonomous roles of fibronectin in cardiovascular development

Laminin β1a controls distinct steps during the establishment of digestive organ laterality

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