Abstract:
:Angiogenesis relies on specialized endothelial tip cells to extend toward guidance cues in order to direct growing blood vessels. Although many of the signaling pathways that control this directional endothelial sprouting are well known, the specific cellular mechanisms that mediate this process remain to be fully elucidated. Here, we show that Polo-like kinase 2 (PLK2) regulates Rap1 activity to guide endothelial tip cell lamellipodia formation and subsequent angiogenic sprouting. Using a combination of high-resolution in vivo imaging of zebrafish vascular development and a human umbilical vein endothelial cell (HUVEC) in vitro cell culture system, we observed that loss of PLK2 function resulted in a reduction in endothelial cell sprouting and migration, whereas overexpression of PLK2 promoted angiogenesis. Furthermore, we discovered that PLK2 may control angiogenic sprouting by binding to PDZ-GEF to regulate RAP1 activity during endothelial cell lamellipodia formation and extracellular matrix attachment. Consistent with these findings, constitutively active RAP1 could rescue the endothelial cell sprouting defects observed in zebrafish and HUVEC PLK2 knockdowns. Overall, these findings reveal a conserved PLK2-RAP1 pathway that is crucial to regulate endothelial tip cell behavior in order to ensure proper vascular development and patterning in vertebrates.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Yang H,Fang L,Zhan R,Hegarty JM,Ren J,Hsiai TK,Gleeson JG,Miller YI,Trejo J,Chi NCdoi
10.1016/j.ydbio.2015.05.011subject
Has Abstractpub_date
2015-08-15 00:00:00pages
49-60issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(15)00280-8journal_volume
404pub_type
杂志文章abstract::Alkaline phosphatase (AP) activity is expressed in the endodermal cell lineage of ascidian embryos beginning at gastrulation. AP expression is resistant to levels of actinomycin D which completely suppress the appearance of other tissue-specific enzyme and morphological markers including acetylcholinesterase (AchE), a...
journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章,评审
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journal_title:Developmental biology
pub_type: 杂志文章,评审
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journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
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journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2009.01.015
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pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1996.0008
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2018.06.004
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.08.029
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2017.02.015
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2004.03.003
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2009.08.006
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journal_title:Developmental biology
pub_type: 杂志文章
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更新日期:1993-09-01 00:00:00
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journal_title:Developmental biology
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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