Cell Reports
Volume 15, Issue 1, 5 April 2016, Pages 158-170
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Article
Single-Cell Lineage Tracing Reveals that Oriented Cell Division Contributes to Trabecular Morphogenesis and Regional Specification

https://doi.org/10.1016/j.celrep.2016.03.012Get rights and content
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Highlights

  • Establish single-cell lineage tracing and whole-heart clearing and imaging

  • Oriented cell division (OCD) and directional migration contribute to trabeculation

  • OCD is an extrinsic asymmetric cell division

  • OCD contributes to trabecular regional specification

Summary

The cardiac trabeculae are sheet-like structures extending from the myocardium that function to increase surface area. A lack of trabeculation causes embryonic lethality due to compromised cardiac function. To understand the cellular and molecular mechanisms of trabecular formation, we genetically labeled individual cardiomyocytes prior to trabeculation via the brainbow multicolor system and traced and analyzed the labeled cells during trabeculation by whole-embryo clearing and imaging. The clones derived from labeled single cells displayed four different geometric patterns that are derived from different patterns of oriented cell division (OCD) and migration. Of the four types of clones, the inner, transmural, and mixed clones contributed to trabecular cardiomyocytes. Further studies showed that perpendicular OCD is an extrinsic asymmetric cell division that putatively contributes to trabecular regional specification. Furthermore, N-Cadherin deletion in labeled clones disrupted the clonal patterns. In summary, our data demonstrate that OCD contributes to trabecular morphogenesis and specification.

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