Regulation of Nodal signaling propagation by receptor interactions and positive feedback

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2022
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Preiß, Hannes
Mörsdorf, David
Soh, Gary H.
Rogers, Katherine W.
Almuedo-Castillo, María
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eLife. eLife Sciences Publications. 2022, 11, e66397. eISSN 2050-084X. Available under: doi: 10.7554/eLife.66397
Zusammenfassung

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.

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ISO 690PREISS, Hannes, Anna C. KÖGLER, David MÖRSDORF, Daniel CAPEK, Gary H. SOH, Katherine W. ROGERS, Hernán MORALES-NAVARRETE, María ALMUEDO-CASTILLO, Patrick MÜLLER, 2022. Regulation of Nodal signaling propagation by receptor interactions and positive feedback. In: eLife. eLife Sciences Publications. 2022, 11, e66397. eISSN 2050-084X. Available under: doi: 10.7554/eLife.66397
BibTex
@article{Prei2022-09-23Regul-58742,
  year={2022},
  doi={10.7554/eLife.66397},
  title={Regulation of Nodal signaling propagation by receptor interactions and positive feedback},
  volume={11},
  journal={eLife},
  author={Preiß, Hannes and Kögler, Anna C. and Mörsdorf, David and Capek, Daniel and Soh, Gary H. and Rogers, Katherine W. and Morales-Navarrete, Hernán and Almuedo-Castillo, María and Müller, Patrick},
  note={Article Number: e66397}
}
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