Open AccessUsp22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta
Author(s) -
Evangelia Koutelou,
Li Wang,
Andreas Schibler,
Hsueh-Ping Chao,
Xi Kuang,
Kevin Lin,
Yue Lu,
Jianjun Shen,
Collene Jeter,
Andrew P. Salinger,
Marenda A. Wilson,
Yi Chun Chen,
Boyko S. Atanassov,
Dean G. Tang,
Sharon Y.R. Dent
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.174037
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , signal transduction , phenotype , placenta , receptor tyrosine kinase , cancer research , stem cell , gene , genetics , fetus , pregnancy
Usp22, a component of the SAGA complex, is over expressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined. We determined that loss of Usp22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system. These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFβ and several receptor tyrosine kinase (RTK) pathways. Usp22 deletion in endothelial cells and pericytes induced from embryonic stem cells also hinders these signaling cascades with detrimental effects on cell survival and differentiation as well as ability to form vessels. Our findings provide new insights to Usp22 functions during development that may offer clues to its role in disease states.