Abstract
The VEGF pathway is critically required for vasculogenesis, the formation of the primary vascular network. It is also required for angiogenesis resulting in sprouting and pruning of vessels to generate mature arborizing structures. The Notch pathway is essential for arterial-venous specification and the maturation of nascent vessels. We have determined that Tspan18, a member of the Tetraspanin family, is expressed in developing vessels but not in mature vasculature in zebrafish and mouse wound healing. Moreover, reduction at Tspan18 level resulted in aberrant vascular patterning, impaired vessel stability and defective arterial-venous specification. Tspan18 deficiency reduced VEGF, VEGFR2, Notch3 and EphrinB2, and increased EphB4, VEGFR3, Semaphorin3, Neuropilin and PlexinD1 expression. Furthermore, vascular defects of Tspan18 deficiency could be rescued by ectopic expression of VEGFR2 and Notch, but not by knockdown of Semaphorin or Plexin. Functional studies showed that knockdown of Tspan18 led to reduced endothelial cell migration, invasion and tube formation. Tspan18 has dynamic expression, regulates vascular development and maturation in the embryo with re-expression in adult life in wound healing.
References
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Apr 4, 1996·Nature·P CarmelietA Nagy
Apr 4, 1996·Nature·N FerraraM W Moore
Feb 1, 1997·Endocrine Reviews·N Ferrara, T Davis-Smyth
Jun 19, 1998·Developmental Biology·M A ThompsonL I Zon
Sep 23, 2000·Nature·P Carmeliet, R K Jain
Oct 2, 2001·Mechanisms of Development·D LiangR Ge
Jun 28, 2002·Cancer Cell·Kari Alitalo, Peter Carmeliet
Jul 12, 2002·Developmental Cell·Nathan D LawsonBrant M Weinstein
Aug 9, 2002·Developmental Biology·Nathan D Lawson, Brant M Weinstein
Aug 27, 2002·Current Biology : CB·Hinrich HabeckUNKNOWN Tübingen 2000 screen consortium
Sep 5, 2002·Nature Reviews. Genetics·Nathan D Lawson, Brant M Weinstein
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Martin E Hemler
Nov 5, 2003·Trends in Immunology·Jacqueline M TarrantMark D Wright
Apr 14, 2004·Journal of Internal Medicine·Peter Carmeliet
Jul 9, 2004·Developmental Cell·Aaron D GitlerJonathan A Epstein
Jul 9, 2004·Developmental Cell·Jesús Torres-VázquezBrant M Weinstein
Oct 22, 2004·Tissue Antigens·M D WrightA B van Spriel
May 11, 2005·Developmental Biology·Hung-Hsiang Yu, Cecilia B Moens
Dec 13, 2005·Experimental Cell Research·Masabumi Shibuya, Lena Claesson-Welsh
Apr 15, 2006·International Journal of Cancer. Journal International Du Cancer·Rizwan MasoodParkash S Gill
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Anna-Karin OlssonLena Claesson-Welsh
Jan 26, 2007·Development·Jonathan D LeslieJulian Lewis
Jan 30, 2007·Nature·Arndt F Siekmann, Nathan D Lawson
Mar 3, 2007·Development·Ryoichiro KageyamaTaeko Kobayashi
Oct 17, 2007·Genes & Development·Cristina Roca, Ralf H Adams
Feb 10, 2009·Trends in Cell Biology·Maria V GelfandChenghua Gu
Feb 17, 2009·Developmental Cell·L-K Phng, Holger Gerhardt
Mar 17, 2009·Circulation Research·Matthew R Swift, Brant M Weinstein
Oct 20, 2009·Cell·Harald J JungeWeilan Ye
Dec 8, 2009·Blood·Ren LiuParkash S Gill