title: Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation.
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.
authors: Division of Biology, California Institute of Technology, 1200 E. California Blvd., MC139-74, Pasadena, CA 91125, USA. Electronic address: hochgreb@caltech.edu.
authors: Tatiana
authors: T
authors: Hochgreb-Hägele
authors: Division of Biology, California Institute of Technology, 1200 E. California Blvd., MC139-74, Pasadena, CA 91125, USA.
authors: Daniel E S
authors: DE
authors: Koo
authors: Division of Biology, California Institute of Technology, 1200 E. California Blvd., MC139-74, Pasadena, CA 91125, USA. Electronic address: mebronner@caltech.edu.
authors: Marianne E
authors: ME
authors: Bronner
mesh_terms: D000423:Alcian Blue; D017398:Alternative Splicing / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000880:Anthraquinones; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D019902:Chondrocytes / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D007568:Jaw / Q000196:embryology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000502:physiology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C000597778:cdkn1a protein, zebrafish; C571228:tp53 protein, zebrafish; C000597777:zinc finger protein 385C, zebrafish; C010078:alizarin; D000423:Alcian Blue
keywords: Cartilage maturation; Neural crest; Ossification; Zebrafish; p53