PUBLICATION
Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish
- Authors
- Hagos, E.G., and Dougan, S.T.
- ID
- ZDB-PUB-070330-39
- Date
- 2007
- Source
- BMC Developmental Biology 7(1): 22 (Journal)
- Registered Authors
- Dougan, Scott T., Hagos, Engda
- Keywords
- none
- MeSH Terms
-
- Animals
- Benzamides/pharmacology
- Benzodioxoles/pharmacology
- Blastula/drug effects
- Body Patterning/genetics*
- Dioxoles/pharmacology
- Endoderm/physiology*
- Imidazoles/pharmacology
- Intracellular Signaling Peptides and Proteins/antagonists & inhibitors
- Intracellular Signaling Peptides and Proteins/genetics*
- Mesoderm/physiology*
- Nodal Signaling Ligands
- Pyridines/pharmacology
- Time Factors
- Zebrafish/embryology*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics*
- PubMed
- 17391517 Full text @ BMC Dev. Biol.
Citation
Hagos, E.G., and Dougan, S.T. (2007) Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish. BMC Developmental Biology. 7(1):22.
Abstract
BACKGROUND: The vertebrate body plan is generated during gastrulation with the formation of the three germ layers. Members of the Nodal-related subclass of the TGF-beta superfamily induce and pattern the mesoderm and endoderm in all vertebrates. In zebrafish, two nodal-related genes, called squint and cyclops, are required in a dosage-dependent manner for the formation of all derivatives of the mesoderm and endoderm. These genes are expressed dynamically during the blastula stages and may have different roles at different times. This question has been difficult to address because conditions that alter the timing of nodal-related gene expression also change Nodal levels. We utilized a pharmacological approach to conditionally inactivate the ALK 4, 5 and 7 receptors during the blastula stages without disturbing earlier signaling activity. This permitted us to directly examine when Nodal signals specify cell types independently of dosage effects. RESULTS: We show that two drugs, SB-431542 and SB-505124, completely block the response to Nodal signals when added to embryos after the mid-blastula transition. By blocking Nodal receptor activity at later stages, we demonstrate that Nodal signaling is required from the mid-to-late blastula period to specify sequentially, the somites, notochord, blood, Kupffers vesicle, hatching gland, heart, and endoderm. Blocking Nodal signaling at late times prevents specification of cell types derived from the embryo margin, but not those from more animal regions. This suggests a linkage between cell fate and length of exposure to Nodal signals. Confirming this, cells exposed to a uniform Nodal dose adopt progressively more marginal fates with increasing lengths of exposure. Finally, cell fate specification is delayed in squint mutants and accelerated when Nodal levels are elevated. CONCLUSIONS: We conclude that (1) Nodal signals are most active during the mid-to-late blastula stages, when nodal-related gene expression and the movement of responding cells are at their most dynamic; (2) Nodal signals specify cell fates along the animal-vegetal axis in a time-dependent manner; (3) cells respond to the total cumulative dose of Nodal signals to which they are exposed, as a function of distance from the source and duration of exposure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping