ZFIN ID: ZDB-PUB-150201-4
Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation
Hochgreb-Hägele, T., Koo, D.E., Bronner, M.E.
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.
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.