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Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates.

PLoS genetics | Oct 3, 2008

The genetic basis of the development and variation of adult form of vertebrates is not well understood. To address this problem, we performed a mutant screen to identify genes essential for the formation of adult skeletal structures of the zebrafish. Here, we describe the phenotypic and molecular characterization of a set of mutants showing loss of adult structures of the dermal skeleton, such as the rays of the fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the ectodysplasin (eda) and ectodysplasin receptor (edar) genes. These genes are frequently mutated in the human hereditary disease hypohidrotic ectodermal dysplasia (HED; OMIM 224900, 305100) that affects the development of integumentary appendages such as hair and teeth. We find mutations in zebrafish edar that affect similar residues as mutated in human cases of HED and show similar phenotypic consequences. eda and edar are not required for early zebrafish development, but are rather specific for the development of adult skeletal and dental structures. We find that the defects of the fins and scales are due to the role of Eda signaling in organizing epidermal cells into discrete signaling centers of the scale epidermal placode and fin fold. Our genetic analysis demonstrates dose-sensitive and organ-specific response to alteration in levels of Eda signaling. In addition, we show substantial buffering of the effect of loss of edar function in different genetic backgrounds, suggesting canalization of this developmental system. We uncover a previously unknown role of Eda signaling in teleosts and show conservation of the developmental mechanisms involved in the formation and variation of both integumentary appendages and limbs. Lastly, our findings point to the utility of adult genetic screens in the zebrafish in identifying essential developmental processes involved in human disease and in morphological evolution.

Pubmed ID: 18833299 RIS Download

Mesh terms: Animals | Body Patterning | Ectodermal Dysplasia | Ectodysplasins | Edar Receptor | Epidermis | Evolution, Molecular | Humans | Mutation | Signal Transduction | Skeleton | Vertebrates | Zebrafish | Zebrafish Proteins

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Ensembl

A collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. The goal of Ensembl is to automatically annotate the genome, integrate this annotation with other available biological data and make the data publicly available via the web. The range of available data has also expanded to include comparative genomics, variation and regulatory data. Ensembl allows users to: upload and analyze data and save it to an Ensembl account; search for a DNA or protein sequence using BLAST or BLAT; fetch desired data from the public database, using the Perl API; download the databases via FTP in FASTA, MySQL and other formats; and mine Ensembl with BioMart and export sequences or tables in text, HTML, or Excel format. The DNA sequences and assemblies used in the Ensembl genebuild are provided by various projects around the world. Ensembl has entered into an agreement with UCSC and NCBI with regard to sequence identifiers in order to improve consistency between the data provided by different genome browsers. The site also links to the Ensembl blog with updates on new species and sequences as they are added to the database.

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European Bioinformatics Institute

A non-profit academic organization for research and services in bioinformatics that provides freely available data from life science experiments, performs basic research in computational biology, and offers an extensive user training programme, supporting researchers in academia and industry. The Institute manages databases of biological data including nucleic acid, protein sequences, and macromolecular structures.

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BOXSHADE 3.21

This server takes a multiple-alignment file in either GCG''s MSF-format or Clustals ALN-format. Sponsors: This resource was supported by the Swiss EMBnet Node Server. Keywords: Server, Multiple-alignment,

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Human BAC Ends Database

The Human BAC Ends Database is a database of sequences from the ends of bacterial artificial chromosome (BAC) clones. A whole genome sequencing approach has been described in a map-as-you-go strategy. The complete sequence of a seed BAC is searched against a BAC end database and the minimally overlapping clones in each direction are selected for sequencing. As coverage increases, BAC end sequences provide samples for whole genome survey. It currently contains 743,000 end sequences from 470,000 clones (20 X clone coverage and 12% sequence coverage), generated by TIGR, UofWashington and CalTech, providing a sequence marker every 5 kb across the genome. The coverage by paired-ends on chromosome 22 is over 5X. The project is funded by DOE.

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Zebrafish Models for Human Development and Disease

ZF-MODELS - Zebrafish Models for Human Development and Disease is an Integrated Project funded by the European Commission as part of its Sixth Framework Programme (EC Contract LSHG-CT-2003-503496). The project started on January 1, 2004 and is scheduled to run over a period of five years. The aim of this project is to exploit the advantages of the zebrafish to produce knowledge, technology and materials in the form of disease models, drug targets and insight into pathways of gene regulation applicable to human development and disease.

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