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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development
Kyle Niessen1, Gu Zhang, John Brady Ridgway
1Department of Molecular Biology, Division of Research, Genentech Inc, South San Francisco, CA 94080, USA.
Blood
|June 25, 2011
Summary
Notch1-Dll4 signaling is crucial for lymphatic development in mice. Blocking this pathway impairs lymphatic vessel formation, wound healing, and lymphangiogenesis.
Area of Science:
- Vascular biology
- Developmental biology
- Signaling pathways
Background:
- Notch signaling is vital for blood vessel development, regulating endothelial differentiation and angiogenesis.
- While Notch pathway components are implicated in lymphatic development, its role in mammals remained unproven.
- Many regulators of blood vessel development also influence lymphatic development.
Purpose of the Study:
- To investigate the role of Notch1-Dll4 signaling in mammalian postnatal lymphatic development.
- To elucidate the molecular mechanisms underlying Notch-mediated lymphatic regulation.
- To assess the impact of Notch1-Dll4 blockade on lymphangiogenesis during wound healing.
Main Methods:
- Utilized function-blocking antibodies against Notch1 and Dll4 in a mouse model.
- Analyzed postnatal lymphatic development, including vessel morphology and lymphatic markers.
- Investigated EphrinB2 expression and VEGFR3/VEGFC signaling.
- Assessed wound closure and lymphangiogenesis in adult mouse skin.
Main Results:
- Notch1-Dll4 blockade led to defective postnatal lymphatic development in mice.
- Down-regulation of EphrinB2 expression and reduced lymphangiogenic sprouting were observed.
- Compromised lymphatic marker expression, vessel dilation, and disorganized mural cell coverage occurred.
- Dll4 blockade impaired wound healing and adult skin lymphangiogenesis.
Conclusions:
- Demonstrates for the first time that Notch1-Dll4 signaling regulates postnatal lymphatic development in mammals.
- Highlights the role of Notch1-Dll4 in controlling EphrinB2 expression and lymphangiogenesis.
- Establishes Notch1-Dll4 signaling as a key regulator of both normal and pathologic lymphangiogenesis.
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