PUBLICATION
Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face
- Authors
- Zuniga, E., Stellabotte, F., and Crump, J.G.
- ID
- ZDB-PUB-100504-15
- Date
- 2010
- Source
- Development (Cambridge, England) 137(11): 1843-1852 (Journal)
- Registered Authors
- Crump, Gage DeKoeyer, Stellabotte, Frank
- Keywords
- Jagged, Notch, Craniofacial, Skeleton, Zebrafish, Dorsoventral patterning
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Base Sequence
- Body Patterning/genetics
- Body Patterning/physiology
- Calcium-Binding Proteins/genetics
- Calcium-Binding Proteins/metabolism*
- DNA Primers/genetics
- Endothelin-1/genetics
- Endothelin-1/metabolism
- Facial Bones/embryology
- Facial Bones/metabolism
- Humans
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism*
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Models, Biological
- Mutation
- Receptor, Notch2/genetics
- Receptor, Notch2/metabolism
- Receptors, Notch/genetics
- Receptors, Notch/metabolism*
- Signal Transduction
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20431122 Full text @ Development
Citation
Zuniga, E., Stellabotte, F., and Crump, J.G. (2010) Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. Development (Cambridge, England). 137(11):1843-1852.
Abstract
The development of the vertebrate face relies on the regionalization of neural crest-derived skeletal precursors along the dorsoventral (DV) axis. Here we show that Jagged-Notch signaling ensures dorsal identity within the hyoid and mandibular components of the facial skeleton by repressing ventral fates. In a genetic screen in zebrafish, we identified a loss-of-function mutation in jagged 1b (jag1b) that results in dorsal expansion of ventral gene expression and partial transformation of the dorsal hyoid skeleton to a ventral morphology. Conversely, misexpression of human jagged 1 (JAG1) represses ventral gene expression and dorsalizes the ventral hyoid and mandibular skeletons. We further show that jag1b is expressed specifically in dorsal skeletal precursors, where it acts through the Notch2 receptor to activate hey1 expression. Whereas Jagged-Notch positive feedback propagates jag1b expression throughout the dorsal domain, Endothelin 1 (Edn1) inhibits jag1b and hey1 expression in the ventral domain. Strikingly, reduction of Jag1b or Notch2 function partially rescues the ventral defects of edn1 mutants, indicating that Edn1 promotes facial skeleton development in part by inhibiting Jagged-Notch signaling in ventral skeletal precursors. Together, these results indicate a novel function of Jagged-Notch signaling in ensuring dorsal identity within broad fields of facial skeletal precursors.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping