Universität zu Köln

Fischer, Boris, Metzger, Manuel, Richardson, Rebecca ORCID: 0000-0002-4701-8713, Knyphausen, Philipp, Ramezani, Thomas ORCID: 0000-0003-4681-7844, Franzen, Rainer, Schmelzer, Elmon, Bloch, Wilhelm, Carney, Thomas J. and Hammerschmidt, Matthias (2014). p53 and TAp63 Promote Keratinocyte Proliferation and Differentiation in Breeding Tubercles of the Zebrafish. PLoS Genet., 10 (1). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

Full text not available from this repository.

Abstract

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that Delta Np63 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fischer, Boris UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Richardson, Rebecca UNSPECIFIED orcid.org/0000-0002-4701-8713 UNSPECIFIED Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramezani, Thomas UNSPECIFIED orcid.org/0000-0003-4681-7844 UNSPECIFIED Franzen, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmelzer, Elmon UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Carney, Thomas J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-450346
DOI:	10.1371/journal.pgen.1004048
Journal or Publication Title:	PLoS Genet.
Volume:	10
Number:	1
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; EPIDERMAL HOMEOSTASIS; TUMOR-SUPPRESSOR; STEM-CELLS; GERM-LINE; IN-VIVO; P63; NOTCH; SKIN; CANCER Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45034