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PMID:11744375

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Citation

Brewer, S, Jiang, X, Donaldson, S, Williams, T and Sucov, HM (2002) Requirement for AP-2alpha in cardiac outflow tract morphogenesis. Mech. Dev. 110:139-49

Abstract

Most developing structures that express the transcription factor gene AP-2alpha are compromised in AP-2alpha mutant mouse embryos. Since the cardiac neural crest population is one prominent site of AP-2alpha expression, and because the neural crest is known to be required for normal cardiac morphogenesis, we have investigated the involvement of AP-2alpha in cardiac development. All AP-2alpha-deficient embryos examined had malformations of the outflow tract of the developing heart: most had double outlet right ventricle, and a small fraction had persistent truncus arteriosus. To visualize AP-2alpha-expressing cells during the period of cardiac morphogenesis, we established a new mutant germline allele in which an IRES-lacZ sequence was inserted by homologous recombination into the AP-2alpha locus. Positive expression was observed in the cardiac neural crest population during the E9.5-10.5 period (as well as in other known domains of AP-2alpha expression previously noted by in situ hybridization studies), and was mostly extinguished by E11.5 when the cardiac neural crest has migrated into the outflow tract of the developing heart. Importantly, the distribution of AP-2alpha-expressing cardiac neural crest appeared to be identical in normal and mutant embryos. From this analysis, we propose that the AP-2alpha gene functions within the neural crest lineage, that AP-2alpha is not required for neural crest cell migration, and that normal AP-2alpha gene function is required prior to E11.5. AP-2alpha may be involved in an interaction between neural crest and surrounding tissues in the subpharyngeal region, thereby promoting normal outflow tract morphogenesis.

Links

PubMed

Keywords

Animals; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; Fetal Heart/embryology; Gene Expression Regulation, Developmental; Lac Operon; Mice; Mice, Knockout; Mice, Transgenic; Neural Crest/embryology; Transcription Factor AP-2; Transcription Factors/deficiency; Transcription Factors/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AP2A

acts_upstream_of_or_within

GO:0003151: outflow tract morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176682

P

Seeded From UniProt

complete


See also

References

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