ZFIN ID: ZDB-PUB-150203-3
The Molecular Regulation of Arteriovenous Specification and Maintenance
Fish, J.E., Wythe, J.D.
Date: 2015
Source: Developmental dynamics : an official publication of the American Association of Anatomists   244(3): 391-409 (Review)
Registered Authors: Fish, Jason E., Wythe, Joshua
Keywords: ETS, Notch, Vegf, artery, vasculogenesis, vein
MeSH Terms:
  • Animals
  • Arteriovenous Malformations/embryology*
  • Arteriovenous Malformations/genetics
  • Arteriovenous Malformations/pathology
  • Disease Models, Animal
  • Humans
  • Mice
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Wnt Signaling Pathway*
PubMed: 25641373 Full text @ Dev. Dyn.
ABSTRACT
The formation of a hierarchical vascular network, composed of arteries, veins and capillaries, is essential for embryogenesis and is required for the production of new functional vasculature in the adult. Elucidating the molecular mechanisms that orchestrate the differentiation of vascular endothelial cells into arterial and venous cell fates is requisite for regenerative medicine, as the directed formation of perfused vessels is desirable in a myriad of pathological settings, such as in diabetes and following myocardial infarction. Additionally, this knowledge will enhance our understanding and treatment of vascular anomalies, such as arteriovenous malformations (AVMs). From studies in vertebrate model organisms, such as mouse, zebrafish and chick, a number of key signaling pathways have been elucidated that are required for the establishment and maintenance of arterial and venous fates. These include the Hedgehog, Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor-β (TGF-β), Wnt and Notch signaling pathways. In addition, a variety of transcription factor families acting downstream of-or in concert with-these signaling networks play vital roles in arteriovenous (AV) specification. These include Notch and Notch-regulated transcription factors (e.g. HEY and HES), SOX factors, Forkhead factors, β-Catenin, ETS factors and COUP-TFII. It is becoming apparent that AV specification is a highly coordinated process that involves the intersection and carefully orchestrated activity of multiple signaling cascades and transcriptional networks. This review will summarize the molecular mechanisms that are involved in the acquisition and maintenance of AV fate, and will highlight some of the limitations in our current knowledge of the molecular machinery that directs AV morphogenesis. This article is protected by copyright. All rights reserved.
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