Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias.

Abstract	Ectodermal dysplasias (EDs) are a group of human pathological conditions characterized by anomalies in organs derived from epithelial-mesenchymal interactions during development. Dlx3 and p63 act as part of the transcriptional regulatory pathways relevant in ectoderm derivatives, and autosomal mutations in either of these genes are associated with human EDs. However, the functional relationship between both proteins is unknown. Here, we demonstrate that Dlx3 is a downstream target of p63. Moreover, we show that transcription of Dlx3 is abrogated by mutations in the sterile alpha-motif (SAM) domain of p63 that are associated with ankyloblepharon-ectodermal dysplasia-clefting (AEC) dysplasias, but not by mutations found in ectrodactylyectodermal dysplasia-cleft lip/palate (EEC), Limb-mammary syndrome (LMS) and split hand-foot malformation (SHFM) dysplasias. Our results unravel aspects of the transcriptional cascade of events that contribute to ectoderm development and pathogenesis associated with p63 mutations.
Authors	Nadezda Radoja, Luisa Guerrini, Nadia Lo Iacono, Giorgio R Merlo, Antonio Costanzo, Wendy C Weinberg, Girolama La Mantia, Viola Calabrò, Maria I Morasso
Journal	Development (Cambridge, England) (Development) Vol. 134 Issue 1 Pg. 13-8 (Jan 2007) ISSN: 0950-1991 [Print] England
PMID	17164413 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References	Distal-less homeobox proteins Homeodomain Proteins Phosphoproteins Trans-Activators Transcription Factors Trp63 protein, mouse
Topics	Animals Cell Line Cell Line, Tumor Chromatin Immunoprecipitation Ectodermal Dysplasia (etiology, genetics) Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins (genetics) Humans Immunohistochemistry Keratinocytes (metabolism) Male Mice Mutation Osteosarcoma (pathology) Phosphoproteins (genetics) Promoter Regions, Genetic Protein Structure, Tertiary Skin (cytology) Trans-Activators (genetics) Transcription Factors (genetics) Transcription, Genetic

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