Unilateral Dampening of Bmp Activity by Nodal Generates Cardiac Left-Right Asymmetry

Veerkamp, Justus; Rudolph, Franziska; Cseresnyés, Zoltán; Priller, Florian; Otten, Cécile; Renz, Marc; Schaefer, Liliana; Abdelilah‐Seyfried, Salim

doi:10.1016/j.devcel.2013.01.026

Cited by 63 publications

(81 citation statements)

References 34 publications

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“…In the context of later heart development, high-resolution imaging in zebrafish has identified a role for BMPs during heart tube rotation; here, asymmetric BMP signaling differentially affects migratory behavior on one side (32)(33)(34). These latter observations, together with our data, implicate BMP signaling in early CPC migration and in cardiac morphogenesis in anamniotes and amniotes, respectively.…”

Section: Discussionsupporting

confidence: 74%

“…This restricts Smad1 activity and facilitates recognition by the ubiquitin ligase Smurf1 (SMAD ubiquitination regulatory factor 1), causing degradation or, alternatively, cytoplasmic retention (24)(25)(26) (29)(30)(31), as well as during the initiation of cardiac looping (32)(33)(34). Thus, we determined whether manipulation of BMP signaling activity would alter the migration behavior of prospective cardiac cells.…”

Section: Significancementioning

confidence: 99%

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Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song

McColl

Camp

et al. 2014

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

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In vertebrate embryos, cardiac progenitor cells (CPCs) undergo long-range migration after emerging from the primitive streak during gastrulation. Together with other mesoderm progenitors, they migrate laterally and then toward the ventral midline, where they form the heart. Signals controlling the migration of different progenitor cell populations during gastrulation are poorly understood. Several pathways are involved in the epithelialto-mesenchymal transition and ingression of mesoderm cells through the primitive streak, including fibroblast growth factors and wingless-type family members (Wnt). Here we focus on early CPC migration and use live video microscopy in chicken embryos to demonstrate a role for bone morphogenetic protein (BMP)/SMA and MAD related (Smad) signaling. We identify an interaction of BMP and Wnt/glycogen synthase kinase 3 beta (GSK3β) pathways via the differential phosphorylation of Smad1. Increased BMP2 activity altered migration trajectories of prospective cardiac cells and resulted in their lateral displacement and ectopic differentiation, as they failed to reach the ventral midline. Constitutively active BMP receptors or constitutively active Smad1 mimicked this phenotype, suggesting a cell autonomous response. Expression of GSK3β, which promotes the turnover of active Smad1, rescued the BMP-induced migration phenotype. Conversely, expression of GSK3β-resistant Smad1 resulted in aberrant CPC migration trajectories. Derepression of GSK3β by dominant negative Wnt3a restored normal migration patterns in the presence of high BMP activity. The data indicate the convergence of BMP and Wnt pathways on Smad1 during the early migration of prospective cardiac cells. Overall, we reveal molecular mechanisms that contribute to the emerging paradigm of signaling pathway integration in embryo development.live imaging | cell tracking

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Section: Discussionsupporting

confidence: 74%

Section: Significancementioning

confidence: 99%

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song

McColl

Camp

et al. 2014

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

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“…For example, it is possible that the effect of the Wnt/BMP perturbations is to alter cell motility in a dose-dependent fashion. Indeed, Wnt/ BMP-regulated cell motility has been observed in a number of other systems (Endo et al, 2005;Veerkamp et al, 2013).…”

Section: Pattern Dynamicsmentioning

confidence: 99%

Mathematically guided approaches to distinguish models of periodic patterning

Hiscock

Megason

2015

Development

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How periodic patterns are generated is an open question. A number of mechanisms have been proposed -most famously, Turing's reactiondiffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples.

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“…300 hearts yielded 660 ng RNA. Next, cDNA was synthesized using M-MLV Reverse transcriptase RNase H(-) and random hexamers according to Manufacturer´s instructions, and RT-qPCR experiments were performed as described 12 . Figure 2B).…”

Section: Isolating Mrna From Dissected Heartsmentioning

confidence: 99%

Large-scale Zebrafish Embryonic Heart Dissection for Transcriptional Analysis

Lombardo

Otten

Abdelilah‐Seyfried

2015

JoVE

Self Cite

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The zebrafish embryonic heart is composed of only a few hundred cells, representing only a small fraction of the entire embryo. Therefore, to prevent the cardiac transcriptome from being masked by the global embryonic transcriptome, it is necessary to collect sufficient numbers of hearts for further analyses. Furthermore, as zebrafish cardiac development proceeds rapidly, heart collection and RNA extraction methods need to be quick in order to ensure homogeneity of the samples. Here, we present a rapid manual dissection protocol for collecting functional/beating hearts from zebrafish embryos. This is an essential prerequisite for subsequent cardiac-specific RNA extraction to determine cardiac-specific gene expression levels by transcriptome analyses, such as quantitative real-time polymerase chain reaction (RT-qPCR). The method is based on differential adhesive properties of the zebrafish embryonic heart compared with other tissues; this allows for the rapid physical separation of cardiac from extracardiac tissue by a combination of fluidic shear force disruption, stepwise filtration and manual collection of transgenic fluorescently labeled hearts. Video LinkThe video component of this article can be found at

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Unilateral Dampening of Bmp Activity by Nodal Generates Cardiac Left-Right Asymmetry

Cited by 63 publications

References 34 publications

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Mathematically guided approaches to distinguish models of periodic patterning

Large-scale Zebrafish Embryonic Heart Dissection for Transcriptional Analysis

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