PUBLICATION
Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish
- Authors
- Robertson, R.A., Knight, H.G., Lipovsky, C., Edwards, H.E., Ren, J., Chi, N.C., Yelon, D.
- ID
- ZDB-PUB-260102-14
- Date
- 2026
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Chi, Neil C., Yelon, Deborah
- Keywords
- Acvr1l, Chordin, Smoothened, Cardiac specification, Islet1, Pacemaker cells
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins*/genetics
- Bone Morphogenetic Proteins*/metabolism
- Cell Differentiation
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Heart*/embryology
- Hedgehog Proteins*/genetics
- Hedgehog Proteins*/metabolism
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Signal Transduction*/physiology
- Wnt Signaling Pathway
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41480663 Full text @ Development
Citation
Robertson, R.A., Knight, H.G., Lipovsky, C., Edwards, H.E., Ren, J., Chi, N.C., Yelon, D. (2026) Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish. Development (Cambridge, England). :.
Abstract
Cardiac pacemaking activity is controlled by specialized cardiomyocytes in the cardiac inflow tract (IFT), but the processes that determine IFT dimensions remain poorly understood. Here, we show that Hedgehog (Hh) signaling limits the number of IFT cardiomyocytes in the embryonic zebrafish heart. Inhibiting Hh signaling, either genetically or pharmacologically, results in an expanded IFT population. In contrast, reducing Bmp signaling decreases the number of IFT cardiomyocytes, while increasing Bmp signaling leads to an excess of IFT cardiomyocytes. Temporal inhibition of each pathway reveals that Hh and Bmp signaling act before myocardial differentiation to regulate IFT size. Simultaneous reduction of both Hh and Bmp signaling yields a relatively normal number of IFT cardiomyocytes, suggesting that these pathways function antagonistically during IFT development. Additionally, epistasis analysis suggests that Bmp signaling acts upstream of Wnt signaling to promote IFT formation, whereas Hh signaling limits IFT size in a Wnt-independent manner. Our results support a model in which Hh signaling restricts the establishment of the IFT progenitor pool, while Bmp signaling drives IFT progenitor specification prior to Wnt-directed IFT differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping