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  • Review Article
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The chicken as a model for large-scale analysis of vertebrate gene function

Key Points

  • The already well-established role of the chicken as an important experimental model is being strengthened by the development of genomic resources and the forthcoming sequencing of its genome.

  • The chicken DT40 cell line and easily-accessible embryos provide unique tools for testing gene function.

  • The high frequency of sequence targeting in chicken DT40 cells offers unrivalled precision for the analysis of cell autonomous gene function.

  • Chicken embryos are readily accessible and an increasing number of sophisticated tools — such as morpholinos and RNA interference — that allow genetic manipulations are being developed.

  • The current availability of chicken genomic resources — such as the high density linkage map, the radiation hybrid mapping panel, the BAC library and an EST database — will allow fuller exploitation of this model in the future, with particular emphasis on the testing of gene function.

Abstract

The chicken has been an important experimental system for developmental biology, immunology and microbiology, having led to many fundamental discoveries. The increase in genomic resources, easy access to the embryo and the application of RNA interference mean that it will be easy and quick to use chick embryos to screen the function of many genes during embryonic development. So, it seems likely that the chicken will increasingly be the system of choice for many vertebrate biologists who are interested in gene function.

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Figure 1: Example of techniques for studying chicken embryos.
Figure 2: Gene Ontology functional assignments to eukaryotic proteomes that have been completely sequenced.

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The ENCODE Project Consortium, Michael P. Snyder, … Richard M. Myers

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Acknowledgements

The authors thank the Biotechnology and Biological Sciences Research Council (BBSRC) for supporting their projects on chicken ESTs.

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DATABASES

ArkDB

aggrecan

CENPC

HPRT

wingless

FURTHER INFORMATION

BBSRC Chicken EST Project

Bursal EST/DT40 web site

East Lansing map

EBI proteome web site

Gene Ontology Consortium

INRA

MRC Gene Service

NIH-funded project to completely sequence the chick genome

OMIM human disease database

PHRAP tool

QTL Analysis Projects

QTL Analysis Projects

QTL Analysis Projects

Roslin ArkDB

Roslin Institute

University of Delaware EST resources

US Department of Agriculture — Agricultural Research Service National Programmes

Wageningen University — Groenen's site

Glossary

RNA INTERFERENCE

(RNAi). A process by which double-stranded RNA specifically silences the expression of homologous genes through degradation of their cognate mRNA.

EXPRESSED SEQUENCE TAG

(EST). A single-pass, short read of complementary DNA that is generated from a transcribed region of the genome.

GENE CONVERSION

A specific type of homologous recombination, which results in non-reciprocal genetic exchange.

POLYDACTYLY

The condition of having more than the normal digits.

VIVIPAROUS

Animals in which the embryo establishes a direct connection with the maternal body.

BURSAL LYMPHOMA

The bursa is a specialized region of the gut in chickens in which the cells that are destined to secrete antibodies undertake characteristic stages of development, including immunoglobulin gene re-arrangements. A bursal lymphoma is a tumour derived from these cells; it is usually generated as a result of transformation with a virus, typically the avian leukosis virus

MICROCELL FUSION

A somatic-cell genetic technique used to transfer one or a small number of chromosomes between cells. Microcells that are generated from the donor cells by incubation in colcemid and cytochalasin are fragmented nuclei that are enclosed in nuclear and plasma membranes and that contain one or a few chromosomes.

CRE/L OX P

A site-specific recombination system derived from the Escherichia coli bacteriophage P1. Two short sequences (loxP sites) are engineered to flank the target DNA. Activation of the Cre recombinase enzyme catalyses recombination between the loxP sites, which leads to the excision of the intervening sequence.

CLASS SWITCHING

The somatic recombination process by which immunoglobulin isotypes are switched to IgG or IgA, without altering antigen specificity.

EUPLOID

A cell or an organism that contains the wild-type number of chromosomes.

SOMATIC HYPERMUTATION

A process that occurs after immunoglobulin gene rearrangement, whereby the base sequences of part of the immunoglobulin variable regions are mutated more frequently than the rest of the genome. This sequence variation is subject to a selection process in the immune system that favours those cells that express immunoglobulins with the highest affinity for antigen.

GASTRULATION

A morphogenetic process that leads to the formation of the mesoderm layer between the endoderm and ectoderm layers and to the formation of embryonic body patterns.

APICAL ECTODERMAL RIDGE

The thickening of the ectoderm at the tip of a developing chick limb bud that is required for bud outgrowth.

NODE

The aggregation of cells found at the anterior end of the primitive streak in chick embryos that acts as an organizing centre to direct development of the embryo.

LIMB-POLARIZING REGION

The cells that lie at the posterior margin of the developing chick limb bud and that produce a signal that specifies their position along the antero-posterior axis of the limb.

NOTOCHORD

A rod-like structure in the dorsal midline of the embryo that runs from the head to the tail beneath the future central nervous system.

ADRENAL MEDULLA

The central region of the adrenal gland.

CALCITONIN

A polypeptide hormone that is produced by C cells in the thyroid gland that causes a reduction of calcium ions in the blood.

CAROTID BODY TYPE I CELL

Hormone secreting cells found in small cellular masses associated with the carotid artery (in the neck), which are involved in controlling blood oxygenation.

NEURAL CREST

The group of cells that are derived from the edges of the neural plate, a forerunner of the central nervous system, that migrate to different regions of the body and that give rise to many cell types, including cells of the peripheral nervous system and pigment cells.

SOMITES

The segmented blocks of the mesoderm that lie on either side of the notochord in the embryo.

RIBOZYME

An RNA molecule with catalytic activity.

MORPHOLINO OLIGONUCLEOTIDE

A DNA analogue in which the bases are linked to a six membered morpholine ring.

PROVIRAL DNA

The DNA copy of a retrovirus.

PLACODE

The localized thickening of ectoderm that forms a neural primordium.

MICROPARTICLE BOMBARDMENT

A technique for delivering nucleic acids into the cells, in which small metal particles coated with nucleic acid are fired into the target tissue using high pressure.

LIPOFECTION

The introduction of DNA into cells through liposomes.

FLUORESCENCE IN SITU HYBRIDIZATION

A technique in which a fluorescently labelled DNA probe is used to detect a particular chromosome or gene with the help of fluorescence microscopy.

PHOSPHOTHIORATE OLIGONUCLEOTIDE

DNA with a modified backbone that is more resistant to nucleases.

GENE BINS

Clustered groups of expressed sequence tags that show extensive regions of identity and are therefore predicted to come from the same transcriptional unit, although they might contain alternatively spliced forms. Hence, there are usually more contigs than gene bins produced through assembly with tools such as PHRAP.

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Brown, W., Hubbard, S., Tickle, C. et al. The chicken as a model for large-scale analysis of vertebrate gene function. Nat Rev Genet 4, 87–98 (2003). https://doi.org/10.1038/nrg998

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