title: AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice.
abstract: The homozygous disruption of the mouse AP-2 gene yields a complex and lethal phenotype that results from defective development of the neural tube, head, and body wall. The severe and pleiotropic developmental abnormalities observed in the knockout mouse suggested that AP-2 may regulate several morphogenic pathways. To uncouple the individual developmental mechanisms that are dependent on AP-2, we have now analyzed chimeric mice composed of both wild-type and AP-2-null cells. The phenotypes obtained from these chimeras indicate that there is an independent requirement for AP-2 in the formation of the neural tube, body wall, and craniofacial skeleton. In addition, these studies reveal that AP-2 exerts a major influence on eye formation, which is a critical new role for AP-2 that was masked previously in the knockout mice. Furthermore, we also have uncovered an unexpected influence of AP-2 on limb pattern formation; this influence is typified by major limb duplications. The range of phenotypes observed in the chimeras displays a significant overlap with those caused by teratogenic levels of retinoic acid, strongly suggesting that AP-2 is an important component of the mechanism of action of this morphogen.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nottoli
authors.forename: S
authors.initials: S
authors.lastname: Hagopian-Donaldson
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Perkins
authors.forename: T
authors.initials: T
authors.lastname: Williams
mesh_terms: D000818:Animals; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005121:Extremities / Q000196:embryology; D005123:Eye / Q000196:embryology; D005145:Face / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors