DeltaNp63 antagonizes p53 to regulate mesoderm induction in Xenopus laevis.
p63, a homolog of the tumor suppressor p53, is critical for the development and maintenance of complex epithelia. The developmentally regulated p63 isoform, DeltaNp63, can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological roles is unclear. Based on our initial finding that the mesoderm-inducing factor activin A is suppressed by DeltaNp63 in human keratinocytes, we investigated the role of DeltaNp63 in regulating mesoderm induction during early Xenopus laevis development. We find that down-regulation of DeltaNp63 by morpholino injection in the early Xenopus embryo potentiates mesoderm formation whereas ectopic expression of DeltaNp63 inhibits mesoderm formation. Furthermore, we show that mesodermal induction after down-regulation of DeltaNp63 is dependent on p53. We propose that a key function for p63 in defining a squamous epithelial phenotype is to actively suppress mesodermal cell fates during early development. Collectively, we show that there is a distinct requirement for different p53 family members during the development of both mesodermal and ectodermal tissues. These findings have implications for the role of p63 and p53 in both development and tumorigenesis of human epithelia.
Barton
Christopher E
CE
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Tahinci
Emilios
E
Barbieri
Christopher E
CE
Johnson
Kimberly N
KN
Hanson
Alison J
AJ
Jernigan
Kristin K
KK
Chen
Tony W
TW
Lee
Ethan
E
Pietenpol
Jennifer A
JA
D028341:Activins / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004625:Embryo, Nonmammalian; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D014157:Transcription Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C488640:TP63 protein, Xenopus; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D028341:Activins