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XB-ART-47030
Dev Cell April 29, 2013; 25 (2): 132-43.

CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway.

Charpentier MS , Christine KS , Amin NM , Dorr KM , Kushner EJ , Bautch VL , Taylor JM , Conlon FL .


Abstract
The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 (CASTOR) in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show that CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1- or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show that CASZ1 is required to directly regulate an EGFL7/RhoA-mediated pathway to promote vertebrate vascular development.

PubMed ID: 23639441
PMC ID: PMC3641863
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aplnr casz1 egfl7 gnl3 kdr npat pecam1 rhoa rps29
Morpholinos: casz1 MO1 casz1 MO2 egfl7 MO1 egfl7 MO2


Article Images: [+] show captions
References [+] :
Baltzinger, Xl erg: expression pattern and overexpression during development plead for a role in endothelial cell differentiation. 2000, Pubmed, Xenbase