Abstract
Precise control of lineage segregation is critical for the development of multicellular organisms, but our quantitative understanding of how variable signaling inputs are integrated to activate lineage-specific gene programs remains limited. Here, we show how precisely two out of eight ectoderm cells adopt neural fates in response to ephrin and FGF signals during ascidian neural induction. In each ectoderm cell, FGF signals activate ERK to a level that mirrors its cell contact surface with FGF-expressing mesendoderm cells. This gradual interpretation of FGF inputs is followed by a bimodal transcriptional response of the immediate early gene, Otx, resulting in its activation specifically in the neural precursors. At low levels of ERK, Otx is repressed by an ETS family transcriptional repressor, ERF2. Ephrin signals are critical for dampening ERK activation levels across ectoderm cells so that only neural precursors exhibit above-threshold levels, evade ERF repression, and “switch on” Otx transcription.
| Original language | English |
|---|---|
| Article number | E10 |
| Pages (from-to) | 2966-2979.e10 |
| Number of pages | 14 |
| Journal | Developmental Cell |
| Volume | 56 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - 8 Nov 2021 |
Bibliographical note
Funding Information:We thank Benoit Godard for micro-wells; Christian Rouvière for a custom-made java plugin for background subtraction in ImageJ; Alex McDougall’s team for pRN3-PH-GFP and Phallusia; Rémi Dumollard for the NLS sequence; Delphine Dauga for manual 3D embryo reconstruction advice; Konner Winkley and Michael Veeman for semi-automated segmentation advice; Emma Farley for Otx enhancers; Brad Davidson for FGFR-Venus; Axel Duchene, Laurent Gilletta, Marie Hagström, and Régis Lasbleiz for animal husbandry; and Carine Barreau and Nathalie Dostatni for encouragement and discussions. The team of H.Y. is supported by the Centre National de la Recherche Scientifique (CNRS), Sorbonne University , the Fondation ARC pour la Recherche sur le Cancer (PJA 20131200223 ), and the Agence Nationale de la Recherche ( ANR-17-CE13-0003-01 ). G.D. is research director at the Belgian “Fonds National pour la Recherche Scientifique (FRS – FNRS).” R.B. is supported by a grant from the Interuniversity Institute of Bioinformatics in Brussels.
Funding Information:
We thank Benoit Godard for micro-wells; Christian Rouvi?re for a custom-made java plugin for background subtraction in ImageJ; Alex McDougall's team for pRN3-PH-GFP and Phallusia; R?mi Dumollard for the NLS sequence; Delphine Dauga for manual 3D embryo reconstruction advice; Konner Winkley and Michael Veeman for semi-automated segmentation advice; Emma Farley for Otx enhancers; Brad Davidson for FGFR-Venus; Axel Duchene, Laurent Gilletta, Marie Hagstr?m, and R?gis Lasbleiz for animal husbandry; and Carine Barreau and Nathalie Dostatni for encouragement and discussions. The team of H.Y. is supported by the Centre National de la Recherche Scientifique (CNRS), Sorbonne University, the Fondation ARC pour la Recherche sur le Cancer (PJA 20131200223), and the Agence Nationale de la Recherche (ANR-17-CE13-0003-01). G.D. is research director at the Belgian ?Fonds National pour la Recherche Scientifique (FRS ? FNRS).? R.B. is supported by a grant from the Interuniversity Institute of Bioinformatics in Brussels. All image acquisitions were conducted in the imaging platform PIM (member of MICA). Our imaging platform (PIM) and animal facility (CRB) are supported by EMBRC-France, whose French state funds are managed by the ANR within the Investments of the Future program under reference ANR-10-INBS-0. Conceptualization, H.Y. C.H. and G.D. with inputs from G.W. S.d.D. C.S. N.H. and R.B.; methodology, H.Y. C.H. G.W. C.S. G.D. and S.d.D.; software, R.B. S.d.D. and G.D.; validation, G.W. S.d.D. C.S. N.H. R.B. G.D. C.H. and H.Y.; formal analysis, C.H. G.W. H.Y. G.D. S.d.D. C.S. and R.B.; investigation, G.W. H.Y. C.H. S.d.D. C.S. G.D. N.H. R.B. K.I. and Y.S.; writing?original draft, C.H. with essential input from H.Y. and G.D.; writing?review and editing, all authors; visualization, C.H. H.Y. G.W. S.d.D. G.D. C.S. and R.B.; funding acquisition, H.Y. and C.H.; supervision, H.Y. C.H. G.D. and S.d.D.; project administration, H.Y. The authors declare no competing interests.
Funding Information:
All image acquisitions were conducted in the imaging platform PIM (member of MICA). Our imaging platform (PIM) and animal facility (CRB) are supported by EMBRC-France, whose French state funds are managed by the ANR within the Investments of the Future program under reference ANR-10-INBS-0.
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