Asymmetric Fate of the Posterior Part of the Second Heart Field Results in Unexpected Left/Right Contributions to Both Poles of the Heart
Rationale: The second heart field (SHF) contains progenitors of all heart chambers, excluding the left ventricle. The SHF is patterned, and the anterior region is known to be destined to form the outflow tract (OFT) and right ventricle.
Objective: To map the fate of the posterior SHF (pSHF).
Methods and Results: We examined the contribution of pSHF cells, labelled by lipophilic dye at 4 to 6 somite stages, to regions of the heart at 20-25 somites, using mouse embryo culture. Cells more cranial in the pSHF contribute to the atrioventricular canal (AVC) and atria, while those more caudal generate the sinus venosus, but there is intermixing of fate throughout the pSHF. Caudal pSHF contributes symmetrically to the sinus venosus but the fate of cranial pSHF is left/right asymmetrical. Left pSHF moves to dorsal left atrium and superior AVC, whereas right pSHF contributes to right atrium, ventral left atrium and inferior AVC. Retrospective clonal analysis shows these relationships between AVC and atria to be clonal, and that right and left progenitors diverge prior to first and second heart lineage separation. Cranial pSHF cells also contribute to the OFT; proximal and distal at 4 somites, and distal only at 6 somites. All OFT destined cells are intermingled with those that will contribute to inflow and AVC.
Conclusions: These observations show asymmetric fate of the pSHF resulting in unexpected left/right contributions to both poles of the heart and can be integrated into a model of the morphogenetic movement of cells during cardiac looping.
- Cardiac progenitor cells
- Embryonic development
- Mouse heart development
- cell fate
- clonal analysis
- left/right asymmetry
- second heart field
- Received April 12, 2012.
- Accepted September 4, 2012.
- Copyright © 2012, American Heart Association