Molecular and Cellular Mechanisms of Vascular Development

Abstract

Blood vessels form an extensive organ system that enables gas exchange, delivers nutrients and removes waste products from tissues and is, therefore, essential for vertebrate life. Blood vessels additionally regulate leukocyte trafficking to support immune system function and transport endocrine hormones for the systemic regulation of physiological processes. During embryonic development, blood vessels also secrete cues that regulate the formation of other organs. To ensure that functional vasculature forms in the embryo, a large number of molecules regulate a wide range of cellular mechanisms that collectively act on the endothelial cells that form the inner lining of all blood vessels. These molecular and cellular mechanisms may be reactivated after birth to induce blood vessel growth that is beneficial by countering tissue ischemia or pathological if excessive or dysfunctional. Understanding developmental blood vessel growth, therefore, provides knowledge that may be used to develop new therapeutic strategies for a range of diseases.

Key Concepts

  • The circulatory system is the first organ to form during vertebrate embryogenesis and is required for the subsequent development of other organs.
  • The circulatory system is the first organ to form during vertebrate embryogenesis.
  • Proper blood vessel growth and remodeling is required for the subsequent development of other organs.
  • Blood vessel development can be studied using the embryonic mouse hindbrain and perinatal mouse retina.
  • Many molecular pathways synergise to regulate blood vessel growth.
  • Elucidating the mechanisms of vascular development may advance novel therapies to treat vascular insufficiency in ischemic diseases.

Keywords: endothelial cell; angiogenesis; vasculogenesis; angioblast; erythromyeloid progenitor; neural progenitor cell; retina; brain; lung; liver; oxygen‐induced retinopathy

Figure 1. Mechanisms of blood vessel growth. (a) Vasculogenesis involves the differentiation of angioblasts into ECs and their coalescence into lumenised vascular structure. (b) Sprouting angiogenesis involves the formation of EC tip cells to drive the extension of new vessel segments from pre‐existing vessels. (c) Intussusceptive angiogenesis occurs when a blood vessel splits into two after ECs migrate to the centre of the vascular lumen to form a pillar that causes the vessel to split. (d) EMP‐derived progenitors in the circulation can insert into the vascular wall to become ECs and thereby extend the vascular surface.
Figure 2. Mouse models of developmental and pathological angiogenesis (a,b) Hindbrain angiogenesis model: (a) Schematic representation of a hindbrain dissection from an E12.5 mouse embryo. (b) Fluorescent micrograph of the SVP of an E12.5 hindbrain labelled with the EC marker isolectin B4 (IB4); scale bar 250 μm. The boxed area is shown at higher magnification on the right‐hand side; scale bar 50 μm. (c,d) Retina angiogenesis model: (c) Schematic representation of a retina dissection from a P7 mouse eye. (d) Fluorescent micrograph of a P7 retina labelled with IB4; scale bar 1 mm. The boxed area is shown at higher magnification on the right‐hand side; scale bar 100 μm. (e,f) OIR neoangiogenesis model: (e) Schematic representation of hyperoxia‐induced vaso‐obliteration on P12 and the subsequent formation of vascular tufts after return to normoxia pn P17. (f) Fluorescent micrograph of a P17 retina labelled with IB4; scale bar 1 mm. The boxed area is shown at higher magnification on the right‐hand side; scale bar 100 μm.
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Bolton, Rebecca, Naylor, Kirsty, and Ruhrberg, Christiana(Aug 2019) Molecular and Cellular Mechanisms of Vascular Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028519]