Tbx1 affects asymmetric cardiac morphogenesis by regulatingPitx2in the secondary heart field

• DOI: 10.1242/dev.02309
• Publication Date: 2006-03-23T23:43:12Z
• Authors: Sonja Nowotschin; Jun Liao; Philip J. Gage; Jonathan A. Epstein; Marina Campione; Bernice E. Morrow
• Keywords: TBX1; PITX2

Individuals with 22q11 deletion syndrome (22q11DS; DiGeorge/velo-cardio-facial syndrome) have multiple congenital malformations, including cardiovascular defects. Most individuals this possess 1.5-3.0 Mb hemizygous 22q11.2 deletions. The T-box transcription factor TBX1, lies within the nested 1.5 interval and is a strong candidate for its etiology. Inactivation of Tbx1 in mouse results neonatal lethality owing to presence single cardiac outflow tract. One important goal understand molecular pathogenesis defects syndrome. However, pathways are still largely unexplored. Here, we show that co-expressed bicoid-like homeodomain Pitx2 secondary heart field cells pharyngeal mesenchyme. In situ hybridization studies Tbx1(-/-) embryos revealed downregulation these cells. To test possible genetic interaction, intercrossed Tbx1(+/-) Pitx2(+/-) mice. Tbx1(+/-); mice died perinatally defects, double outlet right ventricle, atrial ventricular septal all occurring variable penetrance. An enhancer located between exons 4 5 which putative T-half site was identified near an Nkx2.5-binding regulates asymmetric expression Pitx2. We using vitro binds activates synergistic action Nkx2.5. presented study unravel novel Tbx1-Pitx2 pathway linking morphogenesis.