Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium

Di Ai, Wei Liu, Lijiang Ma, Feiyan Dong, Mei Fang Lu, Degang Wang, Michael P. Verzi, Chenleng Cai, Philip J. Gage, Sylvia Evans, Brian L. Black, Nigel A. Brown, James F. Martin

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Current models of left-right asymmetry hold that an early asymmetric signal is generated at the node and transduced to lateral plate mesoderm in a linear signal transduction cascade through the function of the Nodal signaling molecule. The Pitx2 homeobox gene functions at the final stages of this cascade to direct asymmetric morphogenesis of selected organs including the heart. We previously showed that Pitx2 regulated an asymmetric pathway that was independent of cardiac looping suggesting a second asymmetric cardiac pathway. It has been proposed that in the cardiac outflow tract Pitx2 functions in both cardiac neural crest, as a target of canonical Wnt-signaling, and in the mesoderm-derived cardiac second lineage. We used fate mapping, conditional loss of function, and chimera analysis in mice to investigate the role of Pitx2 in outflow tract morphogenesis. Our findings reveal that Pitx2 is dispensable in the cardiac neural crest but functions in second lineage myocardium revealing that this cardiac progenitor field is patterned asymmetrically.

Original languageEnglish
Pages (from-to)437-449
Number of pages13
JournalDevelopmental Biology
Issue number2
StatePublished - 15 Aug 2006
Externally publishedYes


  • Homeobox
  • Left-right asymmetry
  • Secondary heart field


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