Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation

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 p21cip1/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 p21cip1/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.