Regulation of Nodal signaling propagation by receptor interactions and positive feedback
During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can als...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66397 |
| _version_ | 1811198221960085504 |
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| author | Hannes Preiß Anna C Kögler David Mörsdorf Daniel Čapek Gary H Soh Katherine W Rogers Hernán Morales-Navarrete María Almuedo-Castillo Patrick Müller |
| author_facet | Hannes Preiß Anna C Kögler David Mörsdorf Daniel Čapek Gary H Soh Katherine W Rogers Hernán Morales-Navarrete María Almuedo-Castillo Patrick Müller |
| author_sort | Hannes Preiß |
| collection | DOAJ |
| description | During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish. Here, we characterize three Type I (Acvr1) and four Type II (Acvr2) homologs and show that – except for Acvr1c – all receptor-encoding transcripts are maternally deposited and present during zebrafish embryogenesis. We generated mutants and used them together with combinatorial morpholino knockdown and CRISPR F0 knockout (KO) approaches to assess compound loss-of-function phenotypes. We discovered that the Acvr2 homologs function partly redundantly and partially independently of Nodal to pattern the early zebrafish embryo, whereas the Type I receptors Acvr1b-a and Acvr1b-b redundantly act as major mediators of Nodal signaling. By combining quantitative analyses with expression manipulations, we found that feedback-regulated Type I receptors and co-receptors can directly influence the diffusion and distribution of Nodals, providing a mechanism for the spatial restriction of Nodal signaling during germ layer patterning. |
| first_indexed | 2024-04-12T01:28:23Z |
| format | Article |
| id | doaj.art-40338d055d964c1387c3990bfbc5eefa |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:28:23Z |
| publishDate | 2022-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-40338d055d964c1387c3990bfbc5eefa2022-12-22T03:53:34ZengeLife Sciences Publications LtdeLife2050-084X2022-09-011110.7554/eLife.66397Regulation of Nodal signaling propagation by receptor interactions and positive feedbackHannes Preiß0https://orcid.org/0000-0001-6873-9440Anna C Kögler1https://orcid.org/0000-0003-2794-3589David Mörsdorf2https://orcid.org/0000-0001-8982-2155Daniel Čapek3https://orcid.org/0000-0001-5199-9940Gary H Soh4https://orcid.org/0000-0003-0755-6805Katherine W Rogers5https://orcid.org/0000-0001-5700-2662Hernán Morales-Navarrete6https://orcid.org/0000-0002-9578-2556María Almuedo-Castillo7https://orcid.org/0000-0001-6759-5879Patrick Müller8https://orcid.org/0000-0002-0702-6209Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany; University of Konstanz, Konstanz, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany; University of Konstanz, Konstanz, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyUniversity of Konstanz, Konstanz, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany; University of Konstanz, Konstanz, GermanyDuring vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish. Here, we characterize three Type I (Acvr1) and four Type II (Acvr2) homologs and show that – except for Acvr1c – all receptor-encoding transcripts are maternally deposited and present during zebrafish embryogenesis. We generated mutants and used them together with combinatorial morpholino knockdown and CRISPR F0 knockout (KO) approaches to assess compound loss-of-function phenotypes. We discovered that the Acvr2 homologs function partly redundantly and partially independently of Nodal to pattern the early zebrafish embryo, whereas the Type I receptors Acvr1b-a and Acvr1b-b redundantly act as major mediators of Nodal signaling. By combining quantitative analyses with expression manipulations, we found that feedback-regulated Type I receptors and co-receptors can directly influence the diffusion and distribution of Nodals, providing a mechanism for the spatial restriction of Nodal signaling during germ layer patterning.https://elifesciences.org/articles/66397Nodal signalingReceptorsGerm layer patterningGradient formationDiffusion |
| spellingShingle | Hannes Preiß Anna C Kögler David Mörsdorf Daniel Čapek Gary H Soh Katherine W Rogers Hernán Morales-Navarrete María Almuedo-Castillo Patrick Müller Regulation of Nodal signaling propagation by receptor interactions and positive feedback eLife Nodal signaling Receptors Germ layer patterning Gradient formation Diffusion |
| title | Regulation of Nodal signaling propagation by receptor interactions and positive feedback |
| title_full | Regulation of Nodal signaling propagation by receptor interactions and positive feedback |
| title_fullStr | Regulation of Nodal signaling propagation by receptor interactions and positive feedback |
| title_full_unstemmed | Regulation of Nodal signaling propagation by receptor interactions and positive feedback |
| title_short | Regulation of Nodal signaling propagation by receptor interactions and positive feedback |
| title_sort | regulation of nodal signaling propagation by receptor interactions and positive feedback |
| topic | Nodal signaling Receptors Germ layer patterning Gradient formation Diffusion |
| url | https://elifesciences.org/articles/66397 |
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