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Insulin-like growth factor signaling regulates zebrafish lymphatic-vessel development
Wenxuan Chen1, June P Misa1, Caitlin D Herbert1
1Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
Cell Reports
|February 15, 2026
Summary
The insulin-like growth factor (IGF) signaling pathway is crucial for lymphatic vessel development. This study reveals IGF
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Lymphatic endothelial cell (LEC) migration is vital for lymphatic network formation.
- The interaction between cartilage and lymphatic vessels is not well understood.
Purpose of the Study:
- To investigate the role of the insulin-like growth factor (IGF) signaling pathway in zebrafish lymphatic vessel development.
- To identify molecular mechanisms mediating cartilage-lymphatic interactions.
Main Methods:
- Zebrafish model system for studying lymphatic development.
- Gene knockdown and overexpression techniques.
- Analysis of lymphatic vessel morphology and cell migration.
- In vitro migration assays using human induced pluripotent stem cell-derived LECs.
Main Results:
- The medial facial lymphatic (MFL) vessel development depends on hyoid arch cartilage.
- Pregnancy-associated plasma protein A2 (pappa2) mediates cartilage-lymphatic interaction by cleaving IGF-binding proteins (IGFBPs).
- IGF signaling promotes MFL growth in a cell-autonomous manner.
- Human iPSC-derived LECs express IGF1R and respond to IGF2, indicating conserved function.
Conclusions:
- The IGF signaling pathway plays a critical role in zebrafish lymphatic vessel development.
- Pappa2 and IGFBPs are key regulators of the interaction between cartilage and lymphatic vessels.
- IGF signaling is essential for LEC migration and lymphatic network formation.
