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Author Notes:


Conceptualization by J.S., and J.W.; methodology by J.S., and J.W.; investigation by J.S., E.A.P., X.C., and J.W.; formal analysis by J.S., and J.W.; visualization by J.S. and J.W.; writing by J.W.; funding acquisition by J.W; supervision by J.W. All authors commented on the manuscript.

We thank Weilan Lin for fish care and the Developmental Studies Hybridoma Bank for antibodies. Microscopy data for this study were acquired and analyzed using the Microscopy in Medicine Core in Cardiology at Emory.

The authors declare no competing interests.


Research Funding:

This work was supported by a NIH T32 training fellowship (5T32HL007745-28) and by a AHA (23POST1014396) to E.A.P.; grants from NHLBI (R01HL142762) to J.W. The Microscopy in Medicine Core in Cardiology at Emory was supported by NIH grant (P01 HL095070).


  • Animals
  • Hyaluronic Acid
  • Zebrafish
  • Heart
  • Coronary Vessels
  • Neovascularization, Pathologic
  • Morphogenesis

hapln1a <sup>+</sup> cells guide coronary growth during heart morphogenesis and regeneration


Journal Title:

Nature Communications


Volume 14, Number 1


, Pages 3505-3505

Type of Work:

Article | Final Publisher PDF


Although several tissues and chemokines orchestrate coronary formation, the guidance cues for coronary growth remain unclear. Here, we profile the juvenile zebrafish epicardium during coronary vascularization and identify hapln1a + cells enriched with vascular-regulating genes. hapln1a + cells not only envelop vessels but also form linear structures ahead of coronary sprouts. Live-imaging demonstrates that coronary growth occurs along these pre-formed structures, with depletion of hapln1a + cells blocking this growth. hapln1a + cells also pre-lead coronary sprouts during regeneration and hapln1a + cell loss inhibits revascularization. Further, we identify serpine1 expression in hapln1a + cells adjacent to coronary sprouts, and serpine1 inhibition blocks vascularization and revascularization. Moreover, we observe the hapln1a substrate, hyaluronan, forming linear structures along and preceding coronary vessels. Depletion of hapln1a + cells or serpine1 activity inhibition disrupts hyaluronan structure. Our studies reveal that hapln1a + cells and serpine1 are required for coronary production by establishing a microenvironment to facilitate guided coronary growth.

Copyright information:

© The Author(s) 2023

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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