RRC ID 71909
Author Yamada Y, Zhong Y, Miki S, Taura A, Rabbitts TH.
Title The transcription factor complex LMO2/TAL1 regulates branching and endothelial cell migration in sprouting angiogenesis.
Journal Sci Rep
Abstract The transcription factor complex, consisting of LMO2, TAL1 or LYL1, and GATA2, plays an important role in capillary sprouting by regulating VEGFR2, DLL4, and angiopoietin 2 in tip cells. Overexpression of the basic helix-loop-helix transcription factor LYL1 in transgenic mice results in shortened tails. This phenotype is associated with vessel hyperbranching and a relative paucity of straight vessels due to DLL4 downregulation in tip cells by forming aberrant complex consisting of LMO2 and LYL1. Knockdown of LMO2 or TAL1 inhibits capillary sprouting in spheroid-based angiogenesis assays, which is associated with decreased angiopoietin 2 secretion. In the same assay using mixed TAL1- and LYL1-expressing endothelial cells, TAL1 was found to be primarily located in tip cells, while LYL1-expressing cells tended to occupy the stalk position in sprouts by upregulating VEGFR1 than TAL1. Thus, the interaction between LMO2 and TAL1 in tip cells plays a key role in angiogenic switch of sprouting angiogenesis.
Volume 12(1)
Pages 7226
Published 2022-5-4
DOI 10.1038/s41598-022-11297-3
PII 10.1038/s41598-022-11297-3
PMID 35508511
PMC PMC9068620
MeSH Adaptor Proteins, Signal Transducing / metabolism* Angiopoietin-2* Animals Basic Helix-Loop-Helix Transcription Factors / genetics Endothelial Cells LIM Domain Proteins / genetics LIM Domain Proteins / metabolism* Mice Neoplasm Proteins / genetics Neovascularization, Physiologic / genetics T-Cell Acute Lymphocytic Leukemia Protein 1 / genetics
IF 3.998
Mice RBRC01839
DNA material BOSTAL1 (RDB19985) BOSmLYL1 (RDB19986) BOS beta gal (RDB19987)