PUBLICATION
Zebrafish furin mutants reveal intricacies in regulating Endothelin1 signaling in craniofacial patterning
- Authors
- Walker, M.B., Miller, C.T., Talbot, J.C., Stock, D.W., and Kimmel, C.B.
- ID
- ZDB-PUB-060517-6
- Date
- 2006
- Source
- Developmental Biology 295(1): 194-205 (Journal)
- Registered Authors
- Kimmel, Charles B., Miller, Craig T., Stock, David W., Talbot, Jared, Walker, Macie B.
- Keywords
- none
- MeSH Terms
-
- Head/embryology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Male
- Molecular Sequence Data
- Extremities/embryology
- Body Patterning/physiology*
- Endothelin-1/genetics
- Endothelin-1/metabolism*
- Furin/genetics
- Furin/metabolism*
- Gene Expression Regulation, Developmental
- Gene Duplication
- Chromosome Mapping
- Signal Transduction
- Amino Acid Sequence
- Female
- Embryo, Nonmammalian/metabolism
- SOX9 Transcription Factor
- Mutation
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- HMGB Proteins/genetics
- HMGB Proteins/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Animals
- Transcription Factors/genetics
- Transcription Factors/metabolism
- PubMed
- 16678149 Full text @ Dev. Biol.
Citation
Walker, M.B., Miller, C.T., Talbot, J.C., Stock, D.W., and Kimmel, C.B. (2006) Zebrafish furin mutants reveal intricacies in regulating Endothelin1 signaling in craniofacial patterning. Developmental Biology. 295(1):194-205.
Abstract
Endothelin1 (Edn1) signaling promotes ventral character to the facial skeleton. In zebrafish edn1 mutants, the ventral jaw structures are severely reduced and fused to their dorsal counterparts, with a loss of joints that normally form at an intermediate dorsal-ventral position. Loss of function at another locus, sturgeon, also yields joint losses, but only mild reductions in the ventral jaw structures. We show that sturgeon encodes one of two orthologs of Furin present in zebrafish, and that both furin genes may function partially redundantly to activate Edn1 signaling. Supporting this hypothesis, early expression of edn1-dependent genes is downregulated in sturgeon (furinA) mutants. Later in development, expression of most of these genes recovers to near wild-type levels in furinA mutants but not in edn1 mutants. The recovery explains the less severe furinA mutant skeletal phenotype and suggests that late gene expression is dependent on a critical level of Edn1 signaling not present in the more severe edn1 mutants. However, expression defects in the intermediate joint-forming domains in both mutants persist, explaining the joint losses observed later in both mutants. We further show that in both mutants the arches fail to correctly undergo ventral elongation before skeletogenesis begins and propose a model in which this failure is largely responsible for the loss of an Edn1-dependent compartmentation of the arch into the intermediate and ventral domains.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping