Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways.

Autor: Guglielmi L; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK., Heliot C; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK., Kumar S; Advanced Light Microscopy, The Francis Crick Institute, London, NW1 1AT, UK., Alexandrov Y; Advanced Light Microscopy, The Francis Crick Institute, London, NW1 1AT, UK., Gori I; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK., Papaleonidopoulou F; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK., Barrington C; Bioinformatics and Biostatistics Facility, The Francis Crick Institute, London, NW1 1AT, UK., East P; Bioinformatics and Biostatistics Facility, The Francis Crick Institute, London, NW1 1AT, UK., Economou AD; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK., French PMW; Department of Physics, Imperial College London, SW7 2AZ, London, UK., McGinty J; Department of Physics, Imperial College London, SW7 2AZ, London, UK., Hill CS; Developmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK. caroline.hill@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 04; Vol. 12 (1), pp. 6374. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1038/s41467-021-26486-3
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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