The Hippo pathway effector Wwtr1 regulates cardiac wall maturation in zebrafish

Lai, Jason; Collins, Michelle M.; Uribe, Verónica; Jiménez-Amilburu, Vanesa; Günther, Stefan; Maischein, Hans-Martin; Stainier, Didier Y. R.

doi:10.1242/dev.159210

Cited by 33 publications

(48 citation statements)

References 81 publications

(115 reference statements)

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“…We generated new mutant alleles of yap1 and wwtr1 using CRISPR ( Lai et al, 2017 ). yap1 bns19 contains a 41 bp deletion in exon 1, which encodes part of the TEAD binding domain, whereas wwtr1 bns35 contains a 29 bp insertion in exon 2, which encodes part of the WW domain ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

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Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

Kimelman

Smith

Lai

et al. 2017

eLife

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The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the presumptive epidermis and notochord, and play a critical and unexpected role in posterior body extension by regulating Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord. We further find that Yap1 and Wwtr1, also via Fibronectin, have an essential role in the epidermal morphogenesis necessary to form the initial dorsal and ventral fins, a process previously thought to involve bending of an epithelial sheet, but which we now show involves concerted active cell movement. Our results reveal how the Hippo pathway transcriptional program, localized to two specific tissues, acts to control essential morphological events in the vertebrate embryo.

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Section: Resultsmentioning

confidence: 99%

“…The yap1 bns19 and wwtr1 bns35 CRISPR mutant lines are described elsewhere and genotyped as described ( Lai et al, 2017 ). Double mutant yap1 -/- ;wwtr1 -/- embryos were identified by phenotype whereas the sibling embryos had a wild-type phenotype.…”

Section: Methodsmentioning

confidence: 99%

Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

Kimelman

Smith

Lai

et al. 2017

eLife

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“…In addition, cardiac phenotype of these mutants is similar in the sense that they both exhibit CM multilayering, although it is more pronounced and starts at an earlier stage in crb2a mutants. Interestingly, we found that Crb2a immunostaining was mostly gone in wwtr1 mutant hearts (data not shown), suggesting that this reduction in Crb2a expression is causing the mislocalization of adherens junctions in wwtr1 mutant hearts (Lai et al, 2018). In summary, the lack of Crb2a functions in zebrafish CMs, affects their ability to remain in a monolayer, subsequently leading to a lack of trabeculae.…”

Section: Discussionmentioning

confidence: 78%

“…Similarly, wwtr1 mutant CMs in WT ventricles have a preference to enter the trabecular layer (Lai et al, 2018). In addition, cardiac phenotype of these mutants is similar in the sense that they both exhibit CM multilayering, although it is more pronounced and starts at an earlier stage in crb2a mutants.…”

Section: Discussionmentioning

confidence: 89%

The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

Jiménez-Amilburu

Stainier

2018

Preprint

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Summary statementInvestigation of the Crumbs polarity protein Crb2a in zebrafish reveals a novel role in cardiac development via regulation of cell-cell adhesion and apicobasal polarity.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/398909 doi: bioRxiv preprint first posted online Aug. 23, 2018; 3 AbstractTissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential to form a functional ventricular wall. Here we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic, at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes colocalizing with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated by those delaminating. We show that blood flow and Nrg/ErbB2 signaling regulate these Crb2a localization changes. crb2a mutants display a multilayered wall with polarized cardiomyocytes, a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junctions in cardiomyocytes. Importantly, transplantation data show that Crb2a controls trabeculation in a CM-autonomous manner. Altogether, our study reveals a critical role for Crb2a during cardiac development.

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“…In mosaic embryos, we observed that all crb2a mutant CMs in wild-type ventricles become part of the trabecular layer. Similarly, wwtr1 mutant CMs in wild-type ventricles exhibit a preference to enter this layer (Lai et al, 2018). The cardiac phenotypes of wwtr1 and crb2a mutants are similar in the sense that they both exhibit CM multilayering, although it is more pronounced and is observed at an earlier stage in crb2a mutants.…”

Section: Discussionmentioning

confidence: 86%

The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

Jiménez-Amilburu

Stainier

2019

Development

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Tissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential for forming a functional ventricular wall. Here, we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes and colocalizes with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated in the delaminating cardiomyocytes. We show that blood flow and Nrg/ErbB2 signaling regulate Crb2a localization dynamics. crb2a −/− display a multilayered wall with polarized cardiomyocytes: a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junction proteins in cardiomyocytes. Importantly, transplantation data show that Crb2a controls CM behavior in a cell-autonomous manner in the sense that crb2a −/− cardiomyocytes transplanted into wild-type animals were always found in the trabecular layer. In summary, our study reveals a crucial role for Crb2a during cardiac development.

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The Hippo pathway effector Wwtr1 regulates cardiac wall maturation in zebrafish

Cited by 33 publications

References 81 publications

Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1

The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

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