Prox1, master regulator of the lymphatic vasculature phenotype

被引:104
作者
Hong, YK
Detmar, M
机构
[1] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
关键词
Prox1; master regulator; lymphatic vasculature phenotype; lineage-specific differentiation; lymphatic vessels; homeobox gene;
D O I
10.1007/s00441-003-0747-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In contrast to the extensive molecular and functional characterization of blood vascular endothelium, little is known about the mechanisms that control the formation and lineage-specific differentiation and function of lymphatic vessels. The homeobox gene Prox1, the vertebrate homologue of the Drosophila prospero gene, has been recently identified to be required for the induction of lymphatic vascular development from preexisting embryonic veins, and studies in Prox1-deficient mice have confirmed Florence Sabin's original hypothesis about the origin of the lymphatic vascular system from embryonic veins. The recent establishment of cell culture models for the selective propagation of blood vascular and lymphatic endothelial cells, together with the findings that these cells maintain their lineage-specific differentiation in vitro, has led to the discovery that Prox1 expression is sufficient to induce a lymphatic phenotype in blood vascular endothelium. Ectopic expression of Prox1 downregulated blood vascular-associated genes and also upregulated some of the known lymphatic endothelial cell markers. Together, these studies suggest that the blood vascular phenotype represents the default endothelial differentiation and they identify an essential role of Prox1 in the program specifying lymphatic endothelial cell fate.
引用
收藏
页码:85 / 92
页数:8
相关论文
共 48 条
[1]  
Asellius G, 1627, LACTIBUS SIVE LACTEI
[2]  
CHULAGRAFF Q, 1991, DEVELOPMENT, P79
[3]  
Demidenko Z, 2001, DEVELOPMENT, V128, P1359
[4]   THE PROSPERO GENE SPECIFIES CELL FATES IN THE DROSOPHILA CENTRAL-NERVOUS-SYSTEM [J].
DOE, CQ ;
CHULAGRAFF, Q ;
WRIGHT, DM ;
SCOTT, MP .
CELL, 1991, 65 (03) :451-464
[5]  
DOE CQ, 1992, DEVELOPMENT, V116, P855
[6]   Prox1 is differentially localized during lens development [J].
Duncan, MK ;
Cui, WW ;
Oh, DJ ;
Tomarev, SI .
MECHANISMS OF DEVELOPMENT, 2002, 112 (1-2) :195-198
[7]   A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes [J].
Gunn, MD ;
Tangemann, K ;
Tam, C ;
Cyster, JG ;
Rosen, SD ;
Williams, LT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (01) :258-263
[8]   Prospero is a panneural transcription factor that modulates homeodomain protein activity [J].
Hassan, B ;
Li, L ;
Bremer, KA ;
Chang, WR ;
Pinsonneault, J ;
Vaessin, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10991-10996
[9]   Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells [J].
Hirakawa, S ;
Hong, YK ;
Harvey, N ;
Schacht, V ;
Matsuda, K ;
Libermann, T ;
Detmar, M .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (02) :575-586
[10]   ASYMMETRIC SEGREGATION OF THE HOMEODOMAIN PROTEIN PROSPERO DURING DROSOPHILA DEVELOPMENT [J].
HIRATA, J ;
NAKAGOSHI, H ;
NABESHIMA, Y ;
MATSUZAKI, F .
NATURE, 1995, 377 (6550) :627-630