Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium.
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.
Ai
Di
D
Institute of Biosciences and Technology, Texas A and M System, Health Science Center, 2121 Holcombe Blvd, Houston, TX 77030, USA.
Liu
Wei
W
Ma
Lijiang
L
Dong
Feiyan
F
Lu
Mei-Fang
MF
Wang
Degang
D
Verzi
Michael P
MP
Cai
Chenleng
C
Gage
Philip J
PJ
Evans
Sylvia
S
Black
Brian L
BL
Brown
Nigel A
NA
Martin
James F
JF
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009432:Neural Crest / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2
D015415:Biomarkers; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2