PUBLICATION
Regulation of Nodal signaling propagation by receptor interactions and positive feedback
- Authors
- Preiß, H., Kögler, A.C., Mörsdorf, D., Čapek, D., Soh, G.H., Rogers, K.W., Morales-Navarrete, H., Almuedo-Castillo, M., Müller, P.
- ID
- ZDB-PUB-220924-36
- Date
- 2022
- Source
- eLIFE 11: (Journal)
- Registered Authors
- Müller, Patrick, Rogers, Katherine
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Activin Receptors, Type I/genetics
- Activin Receptors, Type I/metabolism
- Animals
- Body Patterning/genetics
- Feedback
- Gene Expression Regulation, Developmental
- Nodal Protein/genetics
- Nodal Protein/metabolism
- Signal Transduction/physiology
- Transforming Growth Factor beta/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 36149406 Full text @ Elife
Citation
Preiß, H., Kögler, A.C., Mörsdorf, D., Čapek, D., Soh, G.H., Rogers, K.W., Morales-Navarrete, H., Almuedo-Castillo, M., Müller, P. (2022) Regulation of Nodal signaling propagation by receptor interactions and positive feedback. eLIFE. 11:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping