Lymphatics in bone arise from pre-existing lymphatics

Marco Monroy, Anna L. McCarter, Devon Hominick, Nina Cassidy, Michael T. Dellinger

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Bones do not normally have lymphatics. However, individuals with generalized lymphatic anomaly (GLA) or Gorham-Stout disease (GSD) develop ectopic lymphatics in bone. Despite growing interest in the development of tissue-specific lymphatics, the cellular origin of bone lymphatic endothelial cells (bLECs) is not known and the development of bone lymphatics has not been fully characterized. Here, we describe the development of bone lymphatics in mouse models of GLA and GSD. Through lineage-tracing experiments, we show that bLECs arise from pre-existing Prox1-positive LECs. We show that bone lymphatics develop in a stepwise manner where regional lymphatics grow, breach the periosteum and then invade bone. We also show that the development of bone lymphatics is impaired in mice that lack osteoclasts. Last, we show that rapamycin can suppress the growth of bone lymphatics in our models of GLA and GSD. In summary, we show that bLECs can arise from pre-existing LECs and that rapamycin can prevent the growth of bone lymphatics.

Original languageEnglish (US)
Article numberdev184291
JournalDevelopment (Cambridge)
Volume147
Issue number21
DOIs
StatePublished - Nov 2020

Keywords

  • Generalized lymphatic anomaly
  • Gorham-Stout disease
  • PIK3CA
  • Rapamycin
  • VEGF-C

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Lymphatics in bone arise from pre-existing lymphatics'. Together they form a unique fingerprint.

Cite this