Specification of arterial, venous, and lymphatic endothelial cells during embryonic development
Identifieur interne : 005607 ( Main/Exploration ); précédent : 005606; suivant : 005608Specification of arterial, venous, and lymphatic endothelial cells during embryonic development
Auteurs : Tsutomu KumeSource :
- Histology and histopathology [ 0213-3911 ] ; 2010.
Abstract
The groundbreaking discovery about arterial and venous expression of ephrinB2 and EphB4, respectively, in early embryonic development has led to a new paradigm for vascular research, providing compelling evidence that arterial and venous endothelial cells are established by genetic mechanisms before circulation begins. For arterial specification, vascular endothelial growth factor (VEGF) induces expression of Notch signaling genes, including
Url:
PubMed: 20238301
PubMed Central: 2899674
Affiliations:
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Le document en format XML
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<series><title level="j">Histology and histopathology</title>
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p id="P1">The groundbreaking discovery about arterial and venous expression of ephrinB2 and EphB4, respectively, in early embryonic development has led to a new paradigm for vascular research, providing compelling evidence that arterial and venous endothelial cells are established by genetic mechanisms before circulation begins. For arterial specification, vascular endothelial growth factor (VEGF) induces expression of Notch signaling genes, including <italic>Notch1</italic>
and its ligand, <italic>Delta-like 4</italic>
(<italic>Dll4</italic>
), and Foxc1 and Foxc2 transcription factors directly regulate Dll4 expression. Upon activation of Notch signaling, the Notch downstream genes, <italic>Hey1/2</italic>
in mice or <italic>gridlock</italic>
in zebrafish, further promote arterial differentiation. On the other hand, the orphan nuclear receptor COUP-TFII is a determinant factor for venous specification by inhibiting expression of arterial specific genes, including <italic>Nrp1</italic>
and <italic>Notch</italic>
. After arterial and venous endothelial cells differentiate, a subpopulation of venous endothelial cells is thought to become competent to acquire lymphatic endothelial cell fate by progressively expressing the transcription factors Sox18 and Prox1 to differentiate into lymphatic endothelial cells. Therefore, it has now evident that arterial-venous cell fate determination and subsequent lymphatic development are regulated by the multi-step regulatory system associated with the key signaling pathways and transcription factors. Furthermore, new signaling molecules as additional regulators in these processes have recently been identified. As the mechanistic basis for a link between signaling pathways and transcriptional networks in arterial, venous and lymphatic endothelial cells begins to be uncovered, it is now time to summarize the literature on this exciting topic and provide perspectives for future research in the field.</p>
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