Early fetal development of lung vasculature.

Abstract

Despite its relevance to a variety of congenital anomalies, the earliest stages of lung vascular development are poorly understood. In other organs, two processes have been identified: vasculogenesis, the development of blood lakes in mesenchyme, and angiogenesis, the branching of new vessels from preexisting ones. In the present study we established the events in the development of the lung's vasculature in Swiss-Weber mouse fetuses between 9 and 20 days gestation, using light microscopy (LM), transmission electron microscopy (TEM), barium-gelatin angiograms, and scanning electron microscopy (SEM) of Mercox (methyl methacrylate) vascular casts. Three features were identified: (1) central sprouting or angiogenesis for up to approximately seven generations (counting the artery to each lung as first generation); (2) the formation of peripheral lakes by vasculogenesis; and (3) the development of communications between the central and peripheral systems. At 9 days gestation, intercellular spaces were apparent in the lung mesenchyme; these were formed by discharge of vesicles from mesenchymal cells, which then regrouped to provide "endothelial" cells lining the spaces. The isolated lakes coalesced to form sinusoidal spaces of irregular profile. At 12 days gestation, the earliest time at which were able to make a cast, sprouting of arteries and veins from the central pulmonary vascular trunks was apparent. Between 13 and 14 days gestation the earliest connection between the peripheral and central spaces was identified. Such connections became more numerous and dense by term. Similar images seen on examination of human fetal lung sections by LM indicated that similar processes occur in the vascular development of the human lung.

Loss of PECAM-1 Function Impairs Alveolarization

“…In the embryo, the vasculature of the lung develops initially from two separate but concurrent processes (9). Peripherally, the capillary network arises through a process of vasculogenesis in which endothelial precursors, recruited to the pulmonary mesenchyme, differentiate and then organize into isolated sinusoidal spaces.…”

“…2d and 5a) is consistent with the putative role of PECAM-1 as a facilitator of EC migration. Consequently, given the importance of vessel formation and remodeling to alveolarization (8,9), the disturbances in alveolar formation resulting from the loss of PECAM-1 function may be directly related to insufficient and/or inefficient angiogenesis due to compromises in PECAM-1-dependent EC function. In addition to disturbances in angiogenesis, at least three other processes should be considered.…”

Conditional pulmonary over-expression of Claudin 6 during embryogenesis delays lung morphogenesis

“…Such pathways include those associated with fibroblast growth factors (Fgfs), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), vascular endothelial growth factors (Vegfs), thyroid transcription factor 1 (TTF-1), and Wnts (Burri, 1984;Cardoso, 2001;Copland and Post, 2004;deMello et al, 1997;Gluck, 1978;Stogsdill et al, 2012;Ten Have-Opbroek, 1991;Torday, 1992). When these or other important genetic pathways are defective or delayed, pulmonary hypoplasia or pulmonary agenesis may occur resulting in abnormally low or absent bronchopulmonary segments and terminal alveoli (Ballard, 1980;Stogsdill et al, 2013).…”

Activation Dynamics and Signaling Properties of Notch3 Receptor in the Developing Pulmonary Artery

“…The initial event in vessel development is the formation of basic tubular structures from endothelial precursors (2). Under the influence of PDGF-␤ and Wnt signaling (3,4), formation of mature vessels occurs by the stepwise recruitment, growth, and differentiation of mesenchymal precursors into a circumferential mural cell layer composed of smooth muscle cells and pericytes (5).…”