p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation

Laurikkala, J., Mikkola, M. L., James, M., Tummers, M., Mills, A. A., Thesleff, I. (2006) p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development, 133 (8). pp. 1553-1563. ISSN 09501991

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URL: https://www.ncbi.nlm.nih.gov/pubmed/16524929
DOI: 10.1242/dev.02325

Abstract

Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and stratification of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (?Np63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal stratification. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with ANp63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, ?-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways.

Item Type: Paper
Uncontrolled Keywords: BMP7 FGF10 FGFR2b Notch1 B-Catenin
Subjects: organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > ectodermal placodes
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > ectodermal placodes > ectodermis
organism description > animal > developmental stage > embryo
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p63
organs, tissues, organelles, cell types and functions > organs types and functions > skin
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 13 Dec 2011 17:35
Last Modified: 02 Feb 2017 17:30
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22849

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