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Peer-reviewedCC BY 4.0Communications Biology

Distinct roles of the Lyve1 lineage in mouse heart development

Abstract

The genetic mouse model Lyve1 Cre is widely used to study lymphatic endothelial cells, but its activity in the embryonic heart has not been comprehensively defined. Here we show that the Lyve1 lineage contributes to multiple cardiovascular cell types, including venous endothelium of the sinus venosus forming coronary vessels, endocardial cells generating complementary coronary territories and valve structures, lymphatic endothelial cells required for cardiac lymphatic development, and tissue-resident macrophages within the embryonic myocardium. Functional perturbations studies show that Notch1 gain-of-function in Lyve1 + lineages disrupts vascular development, whereas Prox1 deletion causes severe edema, blood-filled lymphatics, and perinatal lethality. Mid-gestation mutants exhibit underdeveloped blood-filled lymphatics despite intact blood vasculature, and by late gestation cardiac lymphatics are largely depleted. These findings reveal distinct cardiovascular roles of the Lyve1 lineage and establish Lyve1 Cre as a versatile but non-specific model, underscoring the need for careful interpretation when investigating heart development and regeneration.

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BibTeX
@article{klaourakis2026distinct,
  title = {{Distinct roles of the Lyve1 lineage in mouse heart development}},
  author = {Konstantinos Klaourakis and Shreeya B. Kulkarni and Karolina Zvonickova and Jacinta I. Kalisch-Smith and Nicola Smart and Duncan B. Sparrow and David G. Jackson and Paul R. Riley and Joaquim M. Vieira},
  journal = {Communications Biology},
  year = {2026},
  month = oct,
  doi = {10.1038/s42003-026-11224-6},
  url = {https://www.nature.com/articles/s42003-026-11224-6},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Distinct roles of the Lyve1 lineage in mouse heart development
AU  - Konstantinos Klaourakis
AU  - Shreeya B. Kulkarni
AU  - Karolina Zvonickova
AU  - Jacinta I. Kalisch-Smith
AU  - Nicola Smart
AU  - Duncan B. Sparrow
AU  - David G. Jackson
AU  - Paul R. Riley
AU  - Joaquim M. Vieira
PY  - 2026
DA  - 2026/10/21
JO  - Communications Biology
DO  - 10.1038/s42003-026-11224-6
UR  - https://www.nature.com/articles/s42003-026-11224-6
AB  - The genetic mouse model Lyve1 Cre is widely used to study lymphatic endothelial cells, but its activity in the embryonic heart has not been comprehensively defined. Here we show that the Lyve1 lineage contributes to multiple cardiovascular cell types, including venous endothelium of the sinus venosus forming coronary vessels, endocardial cells generating complementary coronary territories and valve structures, lymphatic endothelial cells required for cardiac lymphatic development, and tissue-resident macrophages within the embryonic myocardium. Functional perturbations studies show that Notch1 gain-of-function in Lyve1 + lineages disrupts vascular development, whereas Prox1 deletion causes severe edema, blood-filled lymphatics, and perinatal lethality. Mid-gestation mutants exhibit underdeveloped blood-filled lymphatics despite intact blood vasculature, and by late gestation cardiac lymphatics are largely depleted. These findings reveal distinct cardiovascular roles of the Lyve1 lineage and establish Lyve1 Cre as a versatile but non-specific model, underscoring the need for careful interpretation when investigating heart development and regeneration.
SN  - 2399-3642
ER  -