The role of AP-2 alpha in the development of the outflow tract and pharyngeal arch arteries

  1. Lookup NU author(s)
  2. Dr Simon Bamforth
  3. Divya Venkatesh
Author(s)Bamforth SD, Venkatesh D, Broadbent C, Schneider JE, Bhattacharya S
Editor(s)
Publication type Conference Proceedings (inc. Abstract)
Conference NameAnnual Scientific Conference of the British Cardiovascular Society
Conference LocationLondon
Year of Conference2009
Date1-3 July 2009
Volume95, Supplement 1
Pages103
ISBN1468201X
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Congenital cardiovascular malformation (CCVM) is the most common birth defect and comprises abnormalities of the outflow tract and the great vessels that develop from the pharyngeal arch arteries. Genetic mutations are implicated in causing CCVM, and transgenic mouse models have been created that develop phenotypes reminiscent of human CCVM. One such model has a targeted inactivation of the transcription factor AP-2 (Tcfap2a). In the mouse AP-2 is expressed in the ectoderm, neural crest and mesenchyme of the pharyngeal arches around the time that the pharyngeal arch arteries are developing. Mice null for Tcfap2a present with cardiovascular defects such as ventricular septal defect (VSD), double-outlet right ventricle (DORV), interrupted aortic arch (IAA) and anomalous right subclavian artery (A-RSA). In this study we wanted to identify tissues in which Tcfap2a is crucial for the correct development of the cardiac outflow tract and pharyngeal arch arteries. To achieve this, Tcfap2a was selectively deleted from those cells in the pharyngeal arches in which it is expressed under normal conditions: the ectoderm, second heart field and neural crest. All mice were backcrossed for several generations onto a C57Bl/6 genetic background. Embryos were collected at E14.5–15.5 and analysed by magnetic resonance imaging and histology to assess cardiovascular developmental abnormalities (table). Initially, embryos homozygous null for Tcfap2a were examined to ascertain the incidence and frequency of CCVM on a C57Bl/6 genetic background. A high incidence of cardiovascular defects, including DORV, VSD, IAA and vascular ring was confirmed (fig). When Tcfap2a was selectively deleted from the pharyngeal ectoderm, A-RSA was observed in three of eight embryos. Deletion of Tcfap2a from the second heart field resulted in one embryo from six examined exhibiting IAA and a vascular ring. When Tcfap2a was deleted from the neural crest, cardiovascular defects were observed in five of nine embryos. Two embryos presented with a VSD alone, one with VSD and transposition of the great arteries and two embryos had A-RSA. Taken together, these results suggest that Tcfap2a is required in multiple tissues to control correct cardiovascular development, as deletion from one cell type or domain is not sufficient to recapitulate fully the cardiovascular phenotype seen in the global Tcfap2a null embryos.
PublisherHeart, BMJ Group
ActionsLink to this publication
Library holdingsSearch Newcastle University Library for this item