Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation

Bressan, Michael; Davis, Patricia M.; Timmer, John R.; Herzlinger, Doris; Matsukawa, Takashi

doi:10.1016/j.ydbio.2008.10.045

Cited by 39 publications

(45 citation statements)

References 64 publications

(67 reference statements)

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“…2A,B) (Isogai et al 2003). In Xenopus, persistent expression of BMP inhibitors from the midline notochord is required for the initial separation of the bilateral dorsal aortae (Bressan et al 2009). It is unclear whether earlier extinguishing of the expression of these inhibitors permits formation of a single tube at an earlier stage in the zebrafish, although this seems a likely possibility.…”

Section: Formation Of Axial Vessels and Initial Specification Of Artementioning

confidence: 99%

Vascular Development in the Zebrafish

Gore¹,

Monzo²,

Young³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

232

166

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The zebrafish has emerged as an excellent vertebrate model system for studying blood and lymphatic vascular development. The small size, external and rapid development, and optical transparency of zebrafish embryos are some of the advantages the zebrafish model system offers. Multiple well-established techniques have been developed for imaging and functionally manipulating vascular tissues in zebrafish embryos, expanding on and amplifying these basic advantages and accelerating use of this model system for studying vascular development. In the past decade, studies performed using zebrafish as a model system have provided many novel insights into vascular development. In this article we discuss the amenability of this model system for studying blood vessel development and review contributions made by this system to our understanding of vascular development.

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Section: Formation Of Axial Vessels and Initial Specification Of Artementioning

confidence: 99%

Vascular Development in the Zebrafish

Gore¹,

Monzo²,

Young³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

232

166

View full text Add to dashboard Cite

show abstract

“…The notochord secretes multiple factors, including the BMP antagonists Noggin (Nog) and Chordin (Chd) as well as Sonic hedgehog (Shh), which participate in specifying the midline of the neural plate (the floor plate) and more broadly pattern the dorsal-ventral embryonic axis (Roelink et al, 1994;Sasai et al, 1994;Smith and Harland, 1992;Zimmerman et al, 1996). While the dorsal midline is the earliest midline region to form and by far the most well studied, other midline structures form later in development in more ventral regions, including the descending aorta, primitive linear heart tube, dorsal and ventral mesenteries that connect the gut tube and its derivatives to the body wall, sternum, umbilicus, urinary bladder, uterus, and external genitalia (Bressan et al, 2009;Davis et al, 2008;Hamilton, 1952;Reese et al, 2004). The mechanisms that position these ventral midline structures and ensure their alignment with the dorsal midline are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Establishment of the Visceral Embryonic Midline Is a Dynamic Process that Requires Bilaterally Symmetric BMP Signaling

et al. 2016

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The vertebrate body plan contains both dorsal and ventral midline structures. While dorsal midline structures have been extensively studied, formation of ventral midline structures, and how they become aligned with the dorsal midline, is a fundamental aspect of vertebrate development that is poorly understood. This study uses the chick dorsal mesentery (DM) as a model for investigating the formation of ventral midline structures. We document formation of the DM by epithelial-to-mesenchymal transition (EMT) and medial ingression of the lateral plate coelomic lining and show that DM positioning is a fundamentally dynamic process regulated by relative levels of bone morphogenetic protein (BMP) signaling in the two sides of the ingressing lateral plate. Disruption of this process causes misalignment of the DM and disturbances during initial stages of lung morphogenesis. Since the dorsal midline is a source of BMP antagonists, these results suggest a mechanism for aligning the dorsal and ventral embryonic midlines.

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“…The pre-fusion-stage notochord creates a zone of vascular inhibition, thereby keeping the dorsal aortae apart (Reese et al, 2004;Bressan et al, 2009). However, these studies do not explain how the notochord allows the dorsal aortae to fuse along it later in development.…”

Section: Developmental Change In Regulatory Activities Of the Notochordmentioning

confidence: 93%

“…Through this mechanism BMP modifies the ability of endothelial cells to respond to vessel forming signals; thus, in the absence of BMP signaling, endothelial cells are blind to VEGF. This could explain why endothelial cells do not arise from or migrate to where Nog and Chrd are expressed, despite the presence of VEGF, FGF2 or SHH (Bressan et al, 2009;Kang et al, 2009;Nimmagadda et al, 2005;Reese et al, 2004). It remains unclear whether BMP signals dorsal aortae fusion by regulating the expression of receptors of positive vascular factors.…”

Section: Research Articlementioning

confidence: 99%

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An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis

et al. 2010

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SUMMARYParacrine signals, both positive and negative, regulate the positioning and remodeling of embryonic blood vessels. In the embryos of mammals and birds, the first major remodeling event is the fusion of bilateral dorsal aortae at the midline to form the dorsal aorta. Although the original bilaterality of the dorsal aortae occurs as the result of inhibitory factors (antagonists of BMP signaling) secreted from the midline by the notochord, it is unknown how fusion is later signaled. Here, we report that dorsal aortae fusion is tightly regulated by a change in signaling by the notochord along the anteroposterior axis. During aortae fusion, the notochord ceases to exert its negative influence on vessel formation. This is achieved by a transcriptional downregulation of negative regulators while positive regulators are maintained at pre-fusion levels. In particular, Chordin, the most abundant BMP antagonist expressed in the notochord prior to fusion, undergoes a dramatic downregulation in an anterior to posterior wave. With inhibitory signals diminished and sustained expression of the positive factors SHH and VEGF at the midline, fusion of the dorsal aortae is signaled. These results demonstrate a novel mechanism by which major modifications of the vascular pattern can occur through modulation of vascular inhibitors without changes in the levels of positive vascular regulators.

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Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation

Cited by 39 publications

References 64 publications

Vascular Development in the Zebrafish

Vascular Development in the Zebrafish

Establishment of the Visceral Embryonic Midline Is a Dynamic Process that Requires Bilaterally Symmetric BMP Signaling

An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis

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