Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways.
Animals
Bone Morphogenetic Proteins
/ metabolism
Embryonic Development
Endoderm
/ metabolism
Gene Knockout Techniques
Mesoderm
/ metabolism
Morphogenesis
Nodal Protein
/ metabolism
Signal Transduction
Smad4 Protein
/ deficiency
Transforming Growth Factor beta
/ metabolism
Zebrafish
/ embryology
Zebrafish Proteins
/ deficiency
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 11 2021
04 11 2021
Historique:
received:
17
03
2021
accepted:
07
10
2021
entrez:
5
11
2021
pubmed:
6
11
2021
medline:
24
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34737283
doi: 10.1038/s41467-021-26486-3
pii: 10.1038/s41467-021-26486-3
pmc: PMC8569018
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
Nodal Protein
0
Smad4 Protein
0
Transforming Growth Factor beta
0
Zebrafish Proteins
0
smad4a protein, zebrafish
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6374Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001095
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001095
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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