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Publication : Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway.

First Author  Bamforth SD Year  2004
Journal  Nat Genet Volume  36
Issue  11 Pages  1189-96
PubMed ID  15475956 Mgi Jnum  J:92872
Mgi Id  MGI:3054669 Doi  10.1038/ng1446
Citation  Bamforth SD, et al. (2004) Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nat Genet 36(11):1189-96
abstractText  Malformations of the septum, outflow tract and aortic arch are the most common congenital cardiovascular defects and occur in mice lacking Cited2, a transcriptional coactivator of TFAP2. Here we show that Cited2(-/-) mice also develop laterality defects, including right isomerism, abnormal cardiac looping and hyposplenia, which are suppressed on a mixed genetic background. Cited2(-/-) mice lack expression of the Nodal target genes Pitx2c, Nodal and Ebaf in the left lateral plate mesoderm, where they are required for establishing laterality and cardiovascular development. CITED2 and TFAP2 were detected at the Pitx2c promoter in embryonic hearts, and they activate Pitx2c transcription in transient transfection assays. We propose that an abnormal Nodal-Pitx2c pathway represents a unifying mechanism for the cardiovascular malformations observed in Cited2(-/-) mice, and that such malformations may be the sole manifestation of a laterality defect.
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