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Updated: Jun 18, 2026
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Isolation of Human Lymphatic Endothelial Cells by Multi-parameter Fluorescence-activated Cell Sorting
Published on: May 1, 2015
ALK1 signaling regulates early postnatal lymphatic vessel development.
Kyle Niessen1, Gu Zhang, John Brady Ridgway
1Department of Tumor Biology and Angiogenesis, Division of Research, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Blood
|November 12, 2009
Summary
Activin receptor-like kinase 1 (ALK1) signaling is crucial for lymphatic development. Blocking ALK1 impairs lymphatic vessel formation and differentiation, offering new therapeutic targets for lymphangiogenesis.
Area of Science:
- Vascular Biology
- Developmental Biology
- Cell Signaling
Background:
- Endothelial cells form distinct blood and lymphatic vascular networks in vertebrates.
- While their morphogenesis differs, common signaling pathways regulate both systems.
- Activin receptor-like kinase 1 (ALK1) is vital for blood vessel development.
Purpose of the Study:
- To investigate the role of ALK1 signaling in lymphatic development.
- To determine if ALK1 influences lymphatic endothelial cell differentiation and vascular remodeling.
- To explore ALK1's interaction with VEGFR3 signaling in lymphatic vessels.
Main Methods:
- Analysis of ALK1 pathway component expression in lymphatic endothelial cells.
- In vitro stimulation of lymphatic endothelial cells with ALK1 ligands.
- In vivo blockade of ALK1 signaling in neonatal mice.
- Assessment of lymphatic development, differentiation, and apoptosis.
Main Results:
- Lymphatic endothelial cells express and respond to ALK1 pathway components.
- ALK1 signaling blockade leads to defective lymphatic development in mice.
- ALK1 regulates lymphatic endothelial cell differentiation, impacting vascular development and remodeling.
- Combined ALK1 and VEGFR3 inhibition increases lymphatic vessel apoptosis.
Conclusions:
- ALK1 signaling plays a novel and critical role in lymphatic development.
- ALK1 regulates lymphatic endothelial cell differentiation and vascular remodeling.
- Targeting the ALK1 pathway may offer new strategies for controlling lymphangiogenesis in diseases.
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