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Noise and robustness downstream of a morphogen gradient : Quantitative approach by imaging transcription dynamics in living embryos

Abstract : During development, cell differentiation frequently occurs upon signaling from gradients of molecules, called morphogens. A simple paradigm to study morphogens is the Bicoid gradient, which determines antero-posterior patterning in fruit fly embryos. This transcription factor allows the rapid expression of its major target gene hunchback, in an anterior domain with a sharp boundary. Using the MS2 system to fluorescently tag RNA in living embryos, we were able to show that the ongoing transcription process at the hunchback promoter is bursty Surprisingly, it takes only 3 minutes, from the first hints of transcription at the anterior to reach steady state with the setting of the sharp expression border in the middle of the embryo. To better understand the role of transcription factors other than Bicoid in this process, I used a two-pronged strategy involving synthetic MS2 reporters combined with the analysis of the hunchback MS2 reporter in various mutant backgrounds. The synthetic reporter approach, indicate that Bicoid is able to activate transcription on its own when bound to the promoter but in a stochastic manner. The binding of Hunchback to the Bicoid-dependent promoter reduces this stochasticity while Caudal might act as a posterior repressor gradient. Altogether, this work provide a new light on the mechanisms insuring a precise transcriptional response downstream of Bicoid.
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  • HAL Id : tel-03139877, version 1

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Carmina Angelica Perez Romero. Noise and robustness downstream of a morphogen gradient : Quantitative approach by imaging transcription dynamics in living embryos. Cellular Biology. Sorbonne Université; McMaster university (Hamilton, Canada), 2019. English. ⟨NNT : 2019SORUS306⟩. ⟨tel-03139877⟩

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