Integrin αV is necessary for gastrulation movements that regulate vertebrate body asymmetry

Ablooglu, Ararat J.; Tkachenko, Eugene; Kang, Jian; Shattil, Sanford J.

doi:10.1242/dev.045310

Cited by 38 publications

(60 citation statements)

References 60 publications

(84 reference statements)

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“…However, in these phenotypes, some DFCs remained capable of interacting with others to form small groups of cells, implying that other factor(s) may contribute to DFC clustering. It has been reported that integrin αV and integrin β1b have a role in DFC clustering (26) and that planar cell polarity signaling regulates cell adhesion between DFCs (27). Additional experiments to clarify the relationship between FGF signaling and integrins or planar cell polarity signaling during DFC cluster formation will be important to understand the entire mechanism underlying DFC cluster formation.…”

Section: Discussionmentioning

confidence: 99%

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Matsui

Thitamadee

Murata

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), a key organ required for the left-right asymmetric body plan in zebrafish, is generated from a cluster of ∼20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering. Cnpy1 positively regulates FGF signals within DFCs, which in turn promote Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left-right asymmetric body plan.left-right patterning | ciliogenesis F ibroblast growth factor (FGF) signaling plays crucial roles in multiple morphogenetic processes of vertebrate development, including gastrulation movement, mesoderm formation, and leftright (LR) patterning (1-3). Because gain or loss of function of FGF signaling results in morphological changes in the embryo, some mechanism must ensure appropriate FGF signal levels in space and time for proper morphogenesis throughout development. FGF effectors acting as positive or negative regulators show a wide range of expression patterns and activities, contributing to the precise regulation of FGF signal activity (1, 4). Although most effectors identified to date act as negative regulators of FGF signaling, a few that positively regulate FGF activity have been reported (1, 4).We recently identified in zebrafish a positive regulator of FGF signaling named canopy1 (cnpy1), which is required for maintenance of the midbrain-hindbrain boundary (MHB) (5). Expression of cnpy1 was restricted to the MHB at late-somitogenesis stages, whereas cnpy1 was broadly distributed in earlier embryos (5) (SI Appendix, Fig. S1A), suggesting an additional role(s) for Cnpy1-mediated FGF signaling beyond the regulation of MHB formation. In this study, we characterize cnpy1 in detail during early zebrafish development and show that a Cnpy1-mediated positive feedback loop of FGF signaling promotes cell cluster formation between dorsal forerunner cells (DFCs) during gastrulation. We also demonstrate that the failure of DFCs to cluster when this FGF positive loop is disrupted eventually leads to Kupffer's vesicle (KV) malformation and randomization of LR asymmetric patterning. Results Positive Feedback Loop of FGF Signaling Mediated by Cnpy1 IsActivated Specifically in DFCs During Zebrafish Gastrulation. To reveal the role of Cnpy1-mediated FGF signaling in ...

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Section: Discussionmentioning

confidence: 99%

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Matsui

Thitamadee

Murata

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Perturb Laterality Organ Development-In a recent study we showed that antisense MO-mediated depletion of the integrin ␣V and ␤1b subunits leads to defective DFC migration during zebrafish gastrulation (12). DFCs are the precursor cells of the KV, a ciliated organ involved in zebrafish left-right body axis specification (20,21) Disorganized DFC migration in ␤1b morphants impedes KV formation, resulting in left-right defects in zebrafish (12).…”

Section: Mrnas That Encode Mutant Integrin ␤1b Cytoplasmic Tailsmentioning

confidence: 99%

“…DFCs are the precursor cells of the KV, a ciliated organ involved in zebrafish left-right body axis specification (20,21) Disorganized DFC migration in ␤1b morphants impedes KV formation, resulting in left-right defects in zebrafish (12). Because integrin ␤ cytoplasmic tails represent a major signaling hub for integrin interaction with cellular proteins involved in integrin signaling (22), we first explored the signaling potential of the integrin ␤1b tail in the DFC-to-KV organization processes by taking advantage of the dominantnegative effects of integrin ␤1b overexpression (22)(23)(24).…”

Section: Mrnas That Encode Mutant Integrin ␤1b Cytoplasmic Tailsmentioning

confidence: 99%

C-terminal COOH of Integrin β1 Is Necessary for β1 Association with the Kindlin-2 Adapter Protein

Fitzpatrick

Shattil

Ablooglu

2014

Journal of Biological Chemistry

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Background: Modulation of integrin/kindlin interactions can lead to human disease pathogenesis. Results: Interaction between integrin ␤1 and the kindlin-2 is mainly governed by the ␤1 C-terminal carboxylate moiety. Conclusion:The interaction chemistry identified here between integrin ␤1 and kindlin-2 appears to represent a novel proteinprotein interaction mode. Significance: The unusual integrin ␤1/kindlin-2 association chemistry sheds new light on this aspect of integrin biology.

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“…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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Integrin αV is necessary for gastrulation movements that regulate vertebrate body asymmetry

Cited by 38 publications

References 60 publications

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

C-terminal COOH of Integrin β1 Is Necessary for β1 Association with the Kindlin-2 Adapter Protein

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

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