Neuropilin-1 balances β8 integrin-activated TGFβ signaling to control sprouting angiogenesis in the brain

Hirota, Shinya; Clements, Thomas P.; Tang, Leung K.; Morales, John E.; Lee, Hye Shin; Oh, S. Paul; Rivera, Gonzalo; Wagner, Daniel S.; McCarty, Joseph H.

doi:10.1242/dev.113746

Cited by 70 publications

(77 citation statements)

References 63 publications

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“…In all cases, lethality and varying degrees of impaired angiogenesis have been observed (24–26). Postnatal endothelial-specific deletion of Nrp1 impairs retinal angiogenesis (27).…”

Section: Neuropilin-related Vascular Phenotypesmentioning

confidence: 99%

“…In the developing brain cortex, Nrp1-deficient endothelial cells expressed increased levels of pSMAD3, indicative of increased TGFβ signaling (26). In line with these findings, deletions of Alk1 or Alk5 in Nrp1-deficient endothelial cells can rescue the tip cell phenotype (24,27).…”

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

“…In line with these findings, deletions of Alk1 or Alk5 in Nrp1-deficient endothelial cells can rescue the tip cell phenotype (24,27). Cultured endothelial cells with Nrp1 knockdown display increased phosphorylation of SMAD2/3 when stimulated with TGFβ (26,27). Nrp1 structural mutants lacking the cytoplasmic domain or PDZ-binding consensus motif have no affect on SMAD2 activation, demonstrating that the Nrp1 extracellular domain is required for TGFβ signal inhibition (27).…”

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

“…Nrp1 structural mutants lacking the cytoplasmic domain or PDZ-binding consensus motif have no affect on SMAD2 activation, demonstrating that the Nrp1 extracellular domain is required for TGFβ signal inhibition (27). Nrp1 aeffect on SMAD1/5/8 remains ambiguous, as one group reported it unaffected in HUVEC with Nrp1 knockdown treated with BMP9 or TGFβ, whereas another group reported increased TGFβ-induced pSMAD1/5/8 in HUVEC with Nrp1 knockdown (26,27). Thus, Nrp1 regulation of TGFβ signaling may be contextually dependent and it remains to be determined if Nrp1 differentially affects Alk1 and Alk5 signaling in endothelial cells.…”

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

“…In this model, activation of LAP-TGFβ by neuroepithelial-derived integrin αvβ8 drives TGFβ signaling in endothelial cells, a process inhibited by endothelial Nrp1 (26). Furthermore, integrin αvβ3 on neuroepithelial cell and endothelial Nrp1 can form a trans-cellular complex between these cells leading to promotion of angiogenesis (26). …”

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

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The expanding role of neuropilin

Kofler

Simons

2016

Current Opinion in Hematology

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Purpose of review Long recognized for its role in regulation of vascular endothelial growth factor (VEGF) signaling, neuropilin (Nrp)1 has emerged as a modulator of additional signaling pathways critical for vascular development and function. Here we review two novel functions of Nrp1 in blood vessels: regulation of transforming growth factor (TGF)β signaling in endothelial cells and regulation of platelet derived growth factor (PDGF) signaling in vascular smooth muscle cells (VSMCs). Recent findings Novel mouse models demonstrate that Nrp1 fulfills vascular functions independent of endothelial VEGF signaling. These include modulation of TGFβ –dependent inhibition of endothelial sprouting during developmental angiogenesis and PDGF signaling in VSMCs during development and disease. Summary Broadening our understanding of how and where Nrp1 functions in the vasculature is critical for the development of targeted therapeutics for cancer and vascular diseases such as atherosclerosis and retinopathies.

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“…In all cases, lethality and varying degrees of impaired angiogenesis have been observed (24–26). Postnatal endothelial-specific deletion of Nrp1 impairs retinal angiogenesis (27).…”

Section: Neuropilin-related Vascular Phenotypesmentioning

confidence: 99%

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

Section: Nrp1 Regulation Of Tgfβ Signalingmentioning

confidence: 99%

See 3 more Smart Citations

The expanding role of neuropilin

Kofler

Simons

2016

Current Opinion in Hematology

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Molecular and Cellular Mechanisms of Vascular Development

Bolton¹,

Naylor²,

Ruhrberg³

2019

Encyclopedia of Life Sciences

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Blood vessels form an extensive organ system that enables gas exchange, delivers nutrients and removes waste products from tissues and is, therefore, essential for vertebrate life. Blood vessels additionally regulate leukocyte trafficking to support immune system function and transport endocrine hormones for the systemic regulation of physiological processes. During embryonic development, blood vessels also secrete cues that regulate the formation of other organs. To ensure that functional vasculature forms in the embryo, a large number of molecules regulate a wide range of cellular mechanisms that collectively act on the endothelial cells that form the inner lining of all blood vessels. These molecular and cellular mechanisms may be reactivated after birth to induce blood vessel growth that is beneficial by countering tissue ischemia or pathological if excessive or dysfunctional. Understanding developmental blood vessel growth, therefore, provides knowledge that may be used to develop new therapeutic strategies for a range of diseases. Key Concepts The circulatory system is the first organ to form during vertebrate embryogenesis and is required for the subsequent development of other organs. The circulatory system is the first organ to form during vertebrate embryogenesis. Proper blood vessel growth and remodeling is required for the subsequent development of other organs. Blood vessel development can be studied using the embryonic mouse hindbrain and perinatal mouse retina. Many molecular pathways synergise to regulate blood vessel growth. Elucidating the mechanisms of vascular development may advance novel therapies to treat vascular insufficiency in ischemic diseases.

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Interactions between neural cells and blood vessels in central nervous system development

Morimoto,

Tabata,

Takahashi

et al. 2023

BioEssays

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The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders.

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Neuropilin-1 balances β8 integrin-activated TGFβ signaling to control sprouting angiogenesis in the brain

Cited by 70 publications

References 63 publications

The expanding role of neuropilin

The expanding role of neuropilin

Molecular and Cellular Mechanisms of Vascular Development

Interactions between neural cells and blood vessels in central nervous system development

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