Requirement for AP-2α in cardiac outflow tract morphogenesis

نویسندگان

  • Stephanie Brewer
  • Xiaobing Jiang
  • Stephanie Donaldson
  • Trevor Williams
  • Henry M. Sucov
چکیده

Most developing structures that express the transcription factor gene AP-2a are compromised in AP-2a mutant mouse embryos. Since the cardiac neural crest population is one prominent site of AP-2a expression, and because the neural crest is known to be required for normal cardiac morphogenesis, we have investigated the involvement of AP-2a in cardiac development. All AP-2a-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-2a-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-2a 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-2a 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-2a-expressing cardiac neural crest appeared to be identical in normal and mutant embryos. From this analysis, we propose that the AP-2a gene functions within the neural crest lineage, that AP-2a is not required for neural crest cell migration, and that normal AP-2a gene function is required prior to E11.5. AP-2a may be involved in an interaction between neural crest and surrounding tissues in the subpharyngeal region, thereby promoting normal outflow tract morphogenesis. q 2002 Elsevier Science Ireland Ltd. All rights reserved.

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عنوان ژورنال:
  • Mechanisms of Development

دوره 110  شماره 

صفحات  -

تاریخ انتشار 2002