p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish

Boris Fischer, Manuel Metzger, Rebecca Richardson, Philipp Knyphausen, Thomas Ramezani, Rainer Franzen, Elmon Schmelzer, Wilhelm Bloch, Thomas J Carney, Matthias Hammerschmidt

Research output: Contribution to journalArticle (Academic Journal)peer-review

24 Citations (Scopus)


p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium.

Original languageEnglish
Pages (from-to)e1004048
JournalPLoS Genetics
Issue number1
Publication statusPublished - Jan 2014


  • Animals
  • Breeding
  • Caspase 3
  • Cell Differentiation
  • Cell Proliferation
  • Keratinocytes
  • Mice
  • Molecular Sequence Data
  • Olfactory Pathways
  • Phosphoproteins
  • Protein Isoforms
  • Receptors, Notch
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Zebrafish
  • Zebrafish Proteins


Dive into the research topics of 'p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish'. Together they form a unique fingerprint.

Cite this