A dominant-negative form of p63 is required for epidermal proliferation in zebrafish.
Epidermal stem cells play a critical role in producing the multilayered vertebrate skin. Products of the p63 gene not only mark the epidermal stem cells, but also are absolutely required for the formation of mammalian epidermis. We find that early zebrafish embryos express a dominant-negative form of p63 (DeltaNp63), which accumulates in the nucleus just as epidermal growth begins. Using antisense morpholino oligonucleotides, we show that DeltaNp63 is needed for epidermal growth and limb development and is specifically required for the proliferation of epidermal cells by inhibiting p53 activity. While the structure of fish epidermis is very different from that of higher vertebrates, our study shows that DeltaNp63 has essential and ancient role in the development of skin.
Lee
Hyunsook
H
Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195, USA.
Kimelman
David
D
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D017124:Conserved Sequence; D004817:Epidermis / Q000196:embryology*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D016158:Genes, p53; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins
C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010750:Phosphoproteins; C488641:Tp63 protein, zebrafish; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D029961:Zebrafish Proteins