Imaging translation dynamics in live embryos reveals spatial heterogeneities

Dufourt, Jérémy; Bellec, Maëlle; Trullo, Antonio; Dejean, Matthieu; Rossi, Sylvain de; Favard, Cyril; Lagha, Mounia

doi:10.1126/science.abc3483

Cited by 52 publications

(67 citation statements)

References 58 publications

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“…2 D). The uniform activation of twi transcription is also corroborated by a recent study that followed live accumulation of Twi and identified an early (within ∼5 min) and even appearance of Twi throughout the mesoderm during NC 14 ( Dufourt et al, 2021 ). The rapid activation of twi expression by Dorsal could be facilitated by the presence of multiple binding sites for the Zelda (Zld) pioneer factor, which clears the regulatory region from nucleosomes ( Sun et al, 2015 ) ( …”

Section: Resultssupporting

confidence: 76%

Generation and timing of graded responses to morphogen gradients

et al. 2021

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Morphogen gradients are known to subdivide a naive cell field into distinct zones of gene expression. Here, we examine whether morphogens can also induce a graded response within such domains. To this end, we explore the role of the Dorsal protein nuclear gradient along the dorsoventral axis in defining the graded pattern of actomyosin constriction that initiates gastrulation in early Drosophila embryos. Two complementary mechanisms for graded accumulation of mRNAs of crucial zygotic Dorsal target genes were identified. First, activation of target-gene expression expands over time from the ventral-most region of high nuclear Dorsal to lateral regions, where the levels are lower, as a result of a Dorsal-dependent activation probability of transcription sites. Thus, sites that are activated earlier will exhibit more mRNA accumulation. Second, once the sites are activated, the rate of RNA Polymerase II loading is also dependent on Dorsal levels. Morphological restrictions require that translation of the graded mRNA be delayed until completion of embryonic cell formation. Such timing is achieved by large introns, which provide a delay in production of the mature mRNAs. Spatio-temporal regulation of key zygotic genes therefore shapes the pattern of gastrulation.

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Section: Resultssupporting

confidence: 76%

Generation and timing of graded responses to morphogen gradients

et al. 2021

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“…The snail-primary-enhancer_MS2 transgene was obtained by amplification of the sna endogenous promoter and primary enhancer using the primers listed in Supplementary Data 1 . The 128XMS2 tag 78 was inserted immediately upstream of the yellow reporter gene sequence of the pbphi-yellow plasmid 17 . The transgenic construct was inserted in the VK0033 landing site (BL9750) using PhiC31 targeted insertion 79 .…”

Section: Methodsmentioning

confidence: 99%

The control of transcriptional memory by stable mitotic bookmarking

et al. 2022

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To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is mediated, in part, by transcription factors (TF) mitotic bookmarking. However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses of Drosophila early embryos, we provide evidence that GAGA pioneer factor (GAF) acts as a stable mitotic bookmarker during zygotic genome activation. We show that, during mitosis, GAF remains associated to a large fraction of its interphase targets, including at cis-regulatory sequences of key developmental genes with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and are bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we report that GAF binding establishes competence for rapid activation upon mitotic exit.

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“…Several transcriptional factors, such as Slug, Twist, and ZEB1, have been reported to play a vital function in EMT (Kurppa et al, 2020;Dufourt et al, 2021;Huang et al, 2021). Slug is one of the critical regulators which lead to EMT and is closely related to cancer metastasis.…”

Section: Proposed Model Of Ppa1 In Breast Cancer Progressionmentioning

confidence: 99%

PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway

Guo

Liang

et al. 2021

Front. Cell Dev. Biol.

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Breast cancer is the most common malignancy among women. Inorganic pyrophosphatase 1 (PPA1) is a multifunctional protein involved in the development of several tumors. However, the role of PPA1 in breast cancer progression remains unclear. In this study, we found that PPA1 was highly expressed in breast cancer compared to its levels in normal breast tissue and that it was correlated with breast cancer clinicopathological characteristics, as well as poor survival in breast cancer patients. Silencing PPA1 restrained breast cancer proliferation and metastasis by regulating Slug-mediated epithelial-mesenchymal transition (EMT). Opposite results were observed following PPA1 overexpression. In addition, investigation of the underlying mechanism demonstrated that PPA1 ablation led to decrease phosphatidylinositol 3 kinase (PI3K) phosphorylation levels and attenuate phosphorylated AKT and glycogen synthase kinase-3 β (GSK3β), while ectopic PPA1 expression had the opposite effects. Moreover, PI3K inhibitors suppress the signaling pathways mediating the effects of PPA1 on breast cancer, resulting in tumor growth and metastasis suppression in vitro and in vivo. In summary, our results verify that PPA1 can act as an activator of PI3K/AKT/GSK3β/Slug-mediated breast cancer progression and that it is a potential therapeutic target for the inhibition of tumor progression.

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Imaging translation dynamics in live embryos reveals spatial heterogeneities

Cited by 52 publications

References 58 publications

Generation and timing of graded responses to morphogen gradients

Generation and timing of graded responses to morphogen gradients

The control of transcriptional memory by stable mitotic bookmarking

PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway

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