PUBLICATION
Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation
- Authors
- Hochgreb-Hägele, T., Koo, D.E., Bronner, M.E.
- ID
- ZDB-PUB-150201-4
- Date
- 2015
- Source
- Developmental Biology 400(1): 23-32 (Journal)
- Registered Authors
- Bronner-Fraser, Marianne
- Keywords
- Cartilage maturation, Neural crest, Ossification, Zebrafish, p53
- MeSH Terms
-
- Alcian Blue
- Alternative Splicing/physiology
- Amino Acid Sequence
- Animals
- Anthraquinones
- Binding Sites/genetics
- Blotting, Western
- Chondrocytes/metabolism
- Chromatin Immunoprecipitation
- Cloning, Molecular
- Cyclin-Dependent Kinase Inhibitor p21/metabolism*
- DNA-Binding Proteins/metabolism*
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/physiology*
- In Situ Hybridization
- Jaw/embryology*
- Jaw/metabolism
- Microscopy, Fluorescence
- Models, Biological
- Molecular Sequence Data
- Osteogenesis/physiology*
- Time Factors
- Tumor Suppressor Protein p53/metabolism*
- Zebrafish/embryology*
- Zebrafish Proteins/metabolism*
- PubMed
- 25636963 Full text @ Dev. Biol.
Citation
Hochgreb-Hägele, T., Koo, D.E., Bronner, M.E. (2015) Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation. Developmental Biology. 400(1):23-32.
Abstract
Jaw formation involves an intricate series of molecular events, whereby a chondrogenic scaffold precedes osteogenesis. The mechanisms coupling timing of cartilage maturation to onset of bone differentiation are poorly understood, particularly for neural crest-derived bones of the head. Here we present a novel zebrafish gene/protein-trap Citrine-fusion line that reveals transient expression of the zinc-finger protein Znf385C in maturing chondrocytes of the jaw. Functional analysis shows that loss of Znf385C disrupts a distinct peak of p21(cip1/waf1) expression in the chondrocytes, as well as causes premature ossification of the zebrafish jaw. We find that Znf385C is expressed as two splice variants which act differentially to activate p21(cip1/waf1) and/or interact with p53 in subcellular compartments. Taken together, the results suggest that Znf385C acts as a developmental switch for p53 function that modulates cell cycle arrest of chondrocytes and regulates timing of jaw cartilage maturation and ossification.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping