Blood Vessel Signals During Development and Beyond

Howard Hughes Medical Institute and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Current Topics in Developmental Biology (Impact Factor: 4.68). 02/2004; 62:1-36. DOI: 10.1016/S0070-2153(04)62001-1
Source: PubMed
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    • "Later on, as development proceeds, additional vascular beds form in order to support the establishment, growth and proper functionality of different organs. At present, it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions (Cleaver, 2004; Aird, 2007). Although a large bulk of data describing the development of the systemic vasculature has accumulated during the past decades (Potente et al., 2011), little is known about the embryonic origins and the molecular mechanisms underlying the formation of organ-specific vessels (Nolan et al., 2013). "
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    ABSTRACT: Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. While it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels, as well as the molecular mechanisms regulating their formation, are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas, and as such represents an ideal model to investigate the early steps of organ-specific vessel formation. Here we show that both arterial and venous components of the subintestinal plexus originate from a pool of specialized angioblasts residing in the floor of the Posterior Cardinal Vein (PCV). Using live imaging of zebrafish embryos, in combination with photoconvertable transgenic reporters, we demonstrate that these angioblasts undergo two phases of migration and differentiation. Initially, a subintestinal vein (SIV) forms and expands ventrally through a bone morphogenetic protein (BMP)-dependent step of collective migration. Concomitantly, a VEGF-dependent shift in the directionality of migration, coupled to the upregulation of arterial markers is observed, which culminates with the generation of the supraintestinal artery (SIA). Altogether our results establish the zebrafish subintestinal plexus as an advantageous model for the study of organ-specific vessel development, and provide new insights into the molecular mechanisms controlling its formation. More broadly, our findings suggest that PCV-specialized angioblasts contribute not only to the formation of the early trunk vasculature, but also to the establishment of late forming-, tissue specific vascular beds.
    Full-text · Article · Nov 2015 · Development
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    • "The later stage of pancreas development includes paracrine VEGF-A signaling, which allows the formation of a branching capillary network in islets and interaction of islets with the circulatory system [16]. Lack of or excess blood vessels in islets do not substantially impair later-stage endocrine pancreas development but do have moderate effects on further development of endocrine cells [22]. These findings suggest that disruption of STAT3 and VEGF-A signaling pathways in the pancreas, along with microvascular alterations, may affect islet formation and, thus, insulin secretory function in vivo. "
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    ABSTRACT: Our previous studies have shown that signal transducer and activator of transcription 3 (STAT3) signaling is important for the development of pancreatic microvasculature via its regulation of vascular endothelial growth factor-A (VEGF-A). Pancreas-specific STAT3-KO mice exhibit glucose intolerance and impaired insulin secretion in vivo, along with microvascular alterations in the pancreas. However, the specific role of STAT3 signaling in the regulation of pancreatic islet development and function is not entirely understood. To investigate the role of STAT3 signaling in the formation and maintenance of pancreatic islets, we studied pancreas-specific STAT3-KO mice. Histological analysis showed that STAT3 deficiency affected pancreatic islet morphology. We found an increased proportion of small-sized islets and a reduced fraction of medium-sized islets, indicating abnormal islet development in STAT3-KO mice. Interestingly, the islet area relative to the whole pancreas area in transgenic and control mice was not significantly different. Immunohistochemical analysis on pancreatic cryosections revealed abnormalities in islet architecture in STAT3-KO mice: the pattern of peripheral distribution of glucagon-positive α-cells was altered. At the same time, islets belonging to different size categories isolated from STAT3-KO mice exhibited normal glucose-stimulated insulin secretion in perifusion experiments in vitro when compared to control mice. Our data demonstrate that STAT3 signaling in the pancreas is required for normal islet formation and/or maintenance. Altered islet size distribution in the KO mice does not result in an impaired islet secretory function in vitro. Therefore, our current study supports that the glucose intolerance and in vivo insulin secretion defect in pancreas-specific STAT3-KO mice is due to altered microvasculature in the pancreas, and not intrinsic beta-cell function.
    Preview · Article · Jul 2013 · PLoS ONE
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    ABSTRACT: In multicellular organisms, vascular tissue is necessary to establish a circulation that delivers nutrients and oxygen, removes waste products, and provides a means for interorgan communication (Risau, 1997). In animals, the vasculature is comprised of blood vessels, which permeate most tissues to ensure sufficient oxygen diffusion. Blood vessels are lined by a specialized cell type called endothelial cells, and, given their ubiquitous presence, it is not surprising that they have evolved functions beyond nutrient and oxygen transport. In recent years, significant progress has been made in describing the reciprocal relationship between the endothelial compartment and its surrounding microenvironment. It is now apparent that endothelial cells provide inductive signals during organ development as well as cell guidance molecules involved in patterning. Conversely, the vasculature responds to cues from the parenchyma that bestow upon it tissue-specific functions. Similar signals function under pathological conditions, where endothelial cells play a critical role in defining the local immune response and provide support for tumor growth. Given their vital importance to tissue survival, many of these mechanisms are being targeted in hopes of limiting tumor growth and ameliorating destructive inflammatory diseases. In this review, we discuss the major advances leading to the current understanding of how endothelial cell interactions may influence development and the adult state. We first focus on relevant advances in vasculogenesis/angiogenesis and the reciprocal signals that function during this process. Then, the mechanisms by which endothelial cells influence organogenesis are highlighted with a final discussion on their relation to pathophysiology, particularly tumorigenesis.
    Preview · Article · Mar 2007 · Developmental Cell
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