Cardiovascular System - Blood Vessel Development
|Embryology - 25 Sep 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Endothelial Progenitors
- 4 Vessel Specification
- 5 Vascular Endothelial Growth Factor
- 6 Regulators of Growth
- 7 Histology
- 8 Capillaries
- 9 Cardiac Blood Vessels
- 10 Abnormalities
- 11 References
- 12 Terms
- 13 External Links
- 14 Glossary Links
Blood develops initially within the core of "blood islands" in the mesoderm. During development, there follows a series of "relocations" of the stem cells to different organs within the embryo. In the adult, these stem cells are located in the bone marrow. At the time when blood first forms, there are no bones!
Note that blood vessel development is tightly coupled to development of other systems for example: osteogenesis (bone formation) that is dependent upon early capillary formation; endocrine development that requires blood vessels for hormone distribution.
| formation of new blood vessels
(endothelium from mesoderm)
| formation of blood vessels from pre-existing vessels|
(occurs in development and adult)
Angioblasts initially form small cell clusters (blood islands) within the embryonic and extraembryonic mesoderm. These blood islands extend and fuse together making a primordial vascular network. Within these islands the peripheral cells form endothelial cells while the core cells form blood cells (haemocytoblasts).
Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Jaroslaw Suchanski, Anna Tejchman, Maciej Zacharski, Aleksandra Piotrowska, Jedrzej Grzegrzolka, Grzegorz Chodaczek, Katarzyna Nowinska, Janusz Rys, Piotr Dziegiel, Claudine Kieda, Maciej Ugorski Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression. PLoS ONE: 2017, 12(9);e0184970 PubMed 28938000
Lin Wang, Wei-Zhi Liu, Ling-Yan Pei, Yu-Shi Ke, Jian Cui, Shu-Chun Li Garidisan: Improving the Quality of Ulcer Healing in Rats with Ulcerative Colitis. Evid Based Complement Alternat Med: 2017, 2017;8721257 PubMed 28928792
Azzeddine Laaraje, Naima El Hafidi, Chafik Mahraoui [A rare cause of exertional dry cough: agenesis of the left pulmonary artery associated with pulmonary hypoplasia]. [Cause rare d'une toux sèche à l'effort: agénésie de l'artère pulmonaire gauche avec hypoplasie pulmonaire.] Pan Afr Med J: 2017, 27;146 PubMed 28904674
Claire A Martin, Parag R Gajendragadkar, Sharad Agarwal Palpitations in a 72-year-old woman. Heart: 2017, 103(19);1554-1555 PubMed 28894011
Barbara Joanna Bałan, Urszula Demkow, Piotr Skopiński, Małgorzata Bychawska, Ewa Skopińska-Różewska, Sławomir Lewicki, Robert Zdanowski The effect of pentoxifylline on L-1 sarcoma tumor growth and angiogenesis in Balb/c mice. Cent Eur J Immunol: 2017, 42(2);131-139 PubMed 28860931
Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen. 
Endothelial Tube Formation
The following data is from a recent review.
|Shh||Loss of Shh results in lack of arterial identity in zebrafish. Shh acts upstream of VEGF.|
|VEGF||VEGF acts downstream of Shh signaling to activate Notch via the PLCγ/ERK pathway in zebrafish. Mutant mice expressing only VEGF188 lack arterial differentiation.|
|Nrp1||Null mice display impaired arterial differentiation. Nrp1 is involved in a positive feedback loop of VEGF signaling.|
|Notch||Notch acts downstream of Shh and VEGF signaling in zebrafish. Notch1; Notch4 mutant mice have abnormal vascular development.|
|Dll4||Null mice lack arterial specification.|
|Dll1||Null mice fail to maintain arterial identity.|
|Hey1/2 (Grl)||Null mice lack arterial specification. Lack of grl in zebrafish results in loss of arterial specification.|
|Foxc1/c2||Foxc1; Foxc2 mutant mice lack arterial specification. Foxc1 and Foxc2 directly regulate Dll4 and Hey2 expression. Foxc1 and Foxc2 are also involved in lymphatic vessel development.|
|Sox7/18||Lack of Sox7/18 results in loss of arterial identity in zebrafish.|
|Snrk-1||Snrk-1 acts downstream or parallel to Notch signaling in zebrafish.|
|Dep1||Dep1 acts upstream of PI3K in arterial specification in zebrafish.|
|Crlr||Shh regulates VEGF activity by controlling crlr expression in zebrafish.|
|EphrinB2||Null mice lack boundaries between arteries and veins. EphrinB2 is involved in lymphatic vascular remodeling and maturation.|
|COUP-TFII||COUP-TFII suppresses arterial cell fate by inhibiting Nrp1 and Notch. COUP-TFII also interacts with Prox1 to regulate lymphatic gene expression.|
|EphB4||Null mice lack boundaries between arteries and veins.|
|Sox18||Null mice fail to specify lymphatic endothelial cells. Sox18 induces Prox1 expression.|
|Prox1||Prox1 induces lymphatic markers and maintains lymphatic cell identity.|
Vascular Endothelial Growth Factor
Growing blood vessels follow a gradient generated by tagret tissues/regions of Vascular Endothelial Growth Factor (VEGF) to establish a vascular bed. Recent findings suggest that Notch signaling acts as an inhibitor for this system, preventing sprouting of blood vessels.
Notch is a transmembrane receptor protein involved in regulating cell differentiation in many developing systems.
|Notch and yolk sac blood vessels model||Vasculogenesis and angiogenesis|
Regulators of Growth
The following data is from a review article on ovary vascular development.
Stimulators of Angiogenisis
Inhibitors of Angiogenisis
Vein Light Microscopy
The entire developing and adult cardiovascular system (blood vessels and heart) is lined by a simple squamous epithelium. (Stain - Haematoxylin Eosin)
A developmental capillary endothelial cell subtype associated with osteogenesis, located at the metaphysis and endosteum of postnatal long bone, that couples angiogenesis with osteogenesis. This endothelial cell subtype expresses the markers CD31/PECAM1 and endomucin (CD31hi Emcnhi).
A newly identified endothelial cell subtype similar to type H in function, supporting osteoblast lineage cells and then gives rise to other endothelial cell subpopulations, but this subtype is found in embryonic and early postnatal long bone.
Cardiac Blood Vessels
Earliest vessels in the heart wall develop subepicardially (beneath the outside surface of the heart) near the apex at Carnegie stage 15, which then extends centripetally and at stage 17 coronary arterial stems communicate with the aortic lumen.
Due to the extensive embryonic, and ongoing, remodelling of the vascular system, there are many different vascular variations and anomalies.
Persistent trigeminal and hypoglossal arteries
- Urs H Langen, Mara E Pitulescu, Jung Mo Kim, Rocio Enriquez-Gasca, Kishor K Sivaraj, Anjali P Kusumbe, Amit Singh, Jacopo Di Russo, M Gabriele Bixel, Bin Zhou, Lydia Sorokin, Juan M Vaquerizas, Ralf H Adams Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat. Cell Biol.: 2017, 19(3);189-201 PubMed 28218908
- Xia Wang, Dongying Chen, Kelley Chen, Ali Jubran, AnnJosette Ramirez, Sophie Astrof Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field. Dev. Biol.: 2017, 421(2);108-117 PubMed 27955943
- Jason E Fish, Joshua D Wythe The Molecular Regulation of Arteriovenous Specification and Maintenance. Dev. Dyn.: 2015; PubMed 25641373
- Tsutomu Kume Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol. Histopathol.: 2010, 25(5);637-46 PubMed 20238301 | PMC2899674
- Per Wasteson, Bengt R Johansson, Tomi Jukkola, Silke Breuer, Levent M Akyürek, Juha Partanen, Per Lindahl Developmental origin of smooth muscle cells in the descending aorta in mice. Development: 2008, 135(10);1823-32 PubMed 18417617
- Frances A High, Min Min Lu, Warren S Pear, Kathleen M Loomes, Klaus H Kaestner, Jonathan A Epstein Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development. Proc. Natl. Acad. Sci. U.S.A.: 2008, 105(6);1955-9 PubMed 18245384
- Morayma Reyes, Arkadiusz Dudek, Balkrishna Jahagirdar, Lisa Koodie, Paul H Marker, Catherine M Verfaillie Origin of endothelial progenitors in human postnatal bone marrow. J. Clin. Invest.: 2002, 109(3);337-46 PubMed 11827993
- Jessica N Copeland, Yi Feng, Naveen K Neradugomma, Patrick E Fields, Jay L Vivian Notch signaling regulates remodeling and vessel diameter in the extraembryonic yolk sac. BMC Dev. Biol.: 2011, 11;12 PubMed 21352545 | BMC Dev Biol.
- Yoh Takuwa, Wa Du, Xun Qi, Yasuo Okamoto, Noriko Takuwa, Kazuaki Yoshioka Roles of sphingosine-1-phosphate signaling in angiogenesis. World J Biol Chem: 2010, 1(10);298-306 PubMed 21537463
- H G Augustin Vascular morphogenesis in the ovary. Baillieres Best Pract Res Clin Obstet Gynaecol: 2000, 14(6);867-82 PubMed 11141338
- Benoit Detry, Françoise Bruyère, Charlotte Erpicum, Jenny Paupert, Françoise Lamaye, Catherine Maillard, Bénédicte Lenoir, Jean-Michel Foidart, Marc Thiry, Agnès Noël Digging deeper into lymphatic vessel formation in vitro and in vivo. BMC Cell Biol.: 2011, 12;29 PubMed 21702933 | PMC3141733 | BMC Cell Biol.
- K Turner, V Navaratnam The positions of coronary arterial ostia. Clin Anat: 1996, 9(6);376-80 PubMed 8915616
- Khaled Menshawi, Jay P Mohr, Jose Gutierrez A Functional Perspective on the Embryology and Anatomy of the Cerebral Blood Supply. J Stroke: 2015, 17(2);144-58 PubMed 26060802 | J Stroke.
Jason E Fish, Joshua D Wythe The Molecular Regulation of Arteriovenous Specification and Maintenance. Dev. Dyn.: 2015; PubMed 25641373
A J Davidson, L I Zon Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis. Curr. Top. Dev. Biol.: 2000, 50;45-60 PubMed 10948449
Kathleen E McGrath, Anne D Koniski, Jeffrey Malik, James Palis Circulation is established in a stepwise pattern in the mammalian embryo. Blood: 2003, 101(5);1669-76 PubMed 12406884
Click on the listed keywords below (used to search the external database) the most current references on Medline will be displayed.
| Cardiovascular System Development See also Heart terms
* splanchnic mesoderm - portion of lateral plate mesoderm closest to the endoderm when coelom forms.
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Cite this page: Hill, M.A. 2017 Embryology Cardiovascular System - Blood Vessel Development. Retrieved September 25, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Blood_Vessel_Development
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