PUBLICATION
Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways
- Authors
- Guglielmi, L., Heliot, C., Kumar, S., Alexandrov, Y., Gori, I., Papaleonidopoulou, F., Barrington, C., East, P., Economou, A.D., French, P.M.W., McGinty, J., Hill, C.S.
- ID
- ZDB-PUB-211106-4
- Date
- 2021
- Source
- Nature communications 12: 6374 (Journal)
- Registered Authors
- Hill, Caroline
- Keywords
- none
- Datasets
- GEO:GSE164574, GEO:GSE162289
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins/metabolism*
- Embryonic Development
- Endoderm/metabolism
- Gene Knockout Techniques
- Mesoderm/metabolism
- Morphogenesis
- Nodal Protein/metabolism*
- Signal Transduction
- Smad4 Protein/deficiency
- Smad4 Protein/genetics
- Smad4 Protein/metabolism*
- Transforming Growth Factor beta/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/growth & development*
- Zebrafish/metabolism
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34737283 Full text @ Nat. Commun.
Citation
Guglielmi, L., Heliot, C., Kumar, S., Alexandrov, Y., Gori, I., Papaleonidopoulou, F., Barrington, C., East, P., Economou, A.D., French, P.M.W., McGinty, J., Hill, C.S. (2021) Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways. Nature communications. 12:6374.
Abstract
The transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-β family ligands, which has implications for diseases where Smad4 is mutated or deleted.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping