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Graded signal inputs to binary cell fate decisions : a quantitative approach based on ascidian neural induction

Abstract : To address how a cell interprets a graded signal to generate a threshold response, I studied the initial step of ascidian neural induction. During this process, four ectoderm cells among sixteen are selected as neural precursors. FGF9/16/20, derived from mesendoderm cells, acts as a neural inducer and activates Otx expression through the ERK pathway. Quantitative measurement of cell surface contacts (CSC) between ectoderm cells and FGF-expressing cells has revealed that each ectoderm cell is exposed to FGF, with neural precursors having the largest area of CSC with FGF-expressing cells. Using quantitative measurements of endogenous ERK activation and Otx expression, we have revealed that each ectoderm cell exhibits a level of ERK activation corresponding to its area of CSC with FGF-expressing mesendoderm cells while Otx expression is restricted to only the four neural precursors. An ephrin ligand is expressed in the ectoderm cells and act antagonistically to FGF signals. In embryos inhibited for ephrin/Eph signals, ERK levels are increased in all ectoderm cells, proportionally to their CSC with the FGF-expressing cells. Under these conditions, the spatial precision of Otx expression is lost with additional ectoderm cells exhibiting Otx expression suggesting that ephrin/Eph signals act to reduce the overall levels of ERK activation, such that the non-neural ectoderm cells remain below the threshold required for Otx activation. We tested this hypothesis by treating embryos, in which ephrin signals were blocked, with low doses of the MEK inhibitor U0126. This treatment was sufficient to re-establish the normal Otx expression profile in the four neural precursors.
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Submitted on : Friday, September 23, 2022 - 1:03:09 AM
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  • HAL Id : tel-03784316, version 1

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Géraldine Williaume. Graded signal inputs to binary cell fate decisions : a quantitative approach based on ascidian neural induction. Development Biology. Sorbonne Université, 2020. English. ⟨NNT : 2020SORUS426⟩. ⟨tel-03784316⟩

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