PUBLICATION
Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation
- Authors
- Tuazon, F.B., Wang, X., Andrade, J.L., Umulis, D., Mullins, M.C.
- ID
- ZDB-PUB-200820-5
- Date
- 2020
- Source
- Cell Reports 32: 108039 (Journal)
- Registered Authors
- Mullins, Mary C.
- Keywords
- BMP signaling, embryonic patterning, gradient, mathematical modeling, morphogen, quantitative imaging, zebrafish
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins/metabolism*
- Glycoproteins/metabolism*
- Intercellular Signaling Peptides and Proteins/metabolism*
- Signal Transduction
- Zebrafish
- PubMed
- 32814043 Full text @ Cell Rep.
Citation
Tuazon, F.B., Wang, X., Andrade, J.L., Umulis, D., Mullins, M.C. (2020) Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation. Cell Reports. 32:108039.
Abstract
A fundamental question in developmental biology is how morphogens, such as bone morphogenetic protein (BMP), form precise signaling gradients to impart positional and functional identity to the cells of the early embryo. We combine rigorous mutant analyses with quantitative immunofluorescence to determine that the proteases Bmp1a and Tolloid spatially restrict the BMP antagonist Chordin in dorsoventral (DV) axial patterning of the early zebrafish gastrula. We show that maternally deposited Bmp1a plays an unexpected and non-redundant role in establishing the BMP signaling gradient, while the Bmp1a/Tolloid antagonist Sizzled is surprisingly dispensable. Combining computational modeling and in vivo analyses with an immobile Chordin construct, we demonstrate that long-range Chordin diffusion is not necessary for BMP gradient formation and DV patterning. Our data do not support a counter-gradient of Chordin and instead favor a Chordin sink, established by Bmp1a and Tolloid, as the primary mechanism that drives BMP gradient formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping