The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment

Abstract

SUMMARYThe formation and lumenization of blood vessels has been studied in some detail, but there is little understanding of the morphogenetic mechanisms by which endothelial cells (ECs) forming large caliber vessels aggregate, align themselves and finally form a lumen that can support blood flow. Here, we focus on the development of the zebrafish common cardinal veins (CCVs), which collect all the blood from the embryo and transport it back to the heart. We show that the angioblasts that eventually form the definitive CCVs become specified as a separate population distinct from the angioblasts that form the lateral dorsal aortae. The subsequent development of the CCVs represents a novel mechanism of vessel formation, during which the ECs delaminate and align along the inner surface of an existing luminal space. Thereby, the CCVs are initially established as open-ended endothelial tubes, which extend as single EC sheets along the flow routes of the circulating blood and eventually enclose the entire lumen in a process that we term 'lumen ensheathment'. Furthermore, we found that the initial delamination of the ECs as well as the directional migration within the EC sheet depend on Cadherin 5 function. By contrast, EC proliferation within the growing CCV is controlled by Vascular endothelial growth factor C, which is provided by circulating erythrocytes. Our findings not only identify a novel mechanism of vascular lumen formation, but also suggest a new form of developmental crosstalk between hematopoietic and endothelial cell lineages.

Cell behaviors and dynamics during angiogenesis

“…This process is seen during the development of the zebrafish common cardinal vein; ECs migrate collectively as a sheet over the blood stream towards the heart and, eventually, ECs at the lateral edges migrate downwards and engulf the lumen (Helker et al, 2013). A similar mechanism has also been described during the formation of the DA in quail embryos (Sato et al, 2010).…”

Development of the lymphatic system: new questions and paradigms

“…In this model, a medial population of lateral plate mesoderm angioblasts first migrates to the midline and forms the DA, and a lateral angioblast population later gives rise to the PCV (Kohli et al, 2013). Additional support for this model came from studies analyzing the formation of the zebrafish lateral dorsal aortae and CCV, which also derive from medial and lateral angioblasts, respectively (Helker et al, 2013). A second model postulates that angioblasts first migrate medially and coalesce to form the DA primordium and then, at ∼17.5 hpf, the first signs of arterial/venous differentiation are observed.…”

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

“…The following zebrafish lines have been described previously: Tg(fli1a:GFP) y1 (Lawson and Weinstein, 2002), Tg(kdrl:Has.HRAS-mCherry) s896 (Chi et al, 2008), Tg(cmyb:EGFP) zf169 (North et al, 2007), Tg la3 , Tg(4xUAS:GFP) hzm3 (Distel et al, 2009), Tg(UAS: lifeactGFP) mu271 (Helker et al, 2013), Tg(UAS:Kaede) rk8 (Hatta et al, 2006), Tg(actb2:loxP-STOP-loxP-DsRed) sd5 (Bertrand et al, 2010), gata2a um27 (Zhu et al, 2011), Tg(lmo2:GFP) zf72 (Zhu et al, 2005), Tg(gata1:DsRed) sd2 and Tg(rag2:GFP) zdf8 (Langenau et al, 2003). For clarity, throughout the text Tg(kdrl:Has.…”