Talk:Cardiovascular System - Lymphatic Development: Difference between revisions

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The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP-based lineage-tracing studies using mouse strains expressing Cre recombinase under the control of the Tie2, Runx1, or Prox1 promoter elements. These studies, together with the analysis of Runx1-mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived lymph sacs, lymphatic endothelial cells sprouted, proliferated, and migrated to give rise to the entire lymphatic vasculature, and that hematopoietic cells did not contribute to the developing lymph sacs. We conclude that the mammalian lymphatic system has a solely venous origin.
The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP-based lineage-tracing studies using mouse strains expressing Cre recombinase under the control of the Tie2, Runx1, or Prox1 promoter elements. These studies, together with the analysis of Runx1-mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived lymph sacs, lymphatic endothelial cells sprouted, proliferated, and migrated to give rise to the entire lymphatic vasculature, and that hematopoietic cells did not contribute to the developing lymph sacs. We conclude that the mammalian lymphatic system has a solely venous origin.
PMID: 17908929
PMID: 17908929
==2006==
===Keystones in lymph node development===
J Anat. 2006 Nov;209(5):585-95.
Blum KS, Pabst R.
Department of Functional and Applied Anatomy, Hannover Medical School, Germany. blum.katrin@mh-hannover.de
Abstract
New molecular markers are constantly increasing our knowledge of developmental processes. In this review article we have attempted to summarize the keystones of lymphoid tissue development in embryonic and pathological conditions. During embryonic lymph node development in the mouse, cells from the anterior cardinal vein start to bud and sprout, forming a lymph sac at defined sites. The protrusion of mesenchymal tissue into the lymph sacs forms the environment, where so-called 'lymphoid tissue inducer cells' and 'mesenchymal organizer cells' meet and interact. Defects of molecules involved in the recruitment and signalling cascades of these cells lead to primary immunodeficiency diseases. A comparison of molecules involved in the development of secondary lymphoid organs and tertiary lymphoid organs, e.g. in autoimmune diseases, shows that the same molecules are involved in both processes. This has led to the hypothesis that the development of tertiary lymphoid organs is a recapitulation of embryonic lymphoid tissue development at ectopic sites.
PMID: 17062017


==1986==
==1986==

Revision as of 00:58, 22 February 2011

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Cite this page: Hill, M.A. (2024, March 28) Embryology Cardiovascular System - Lymphatic Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Cardiovascular_System_-_Lymphatic_Development

2010

The embryonic origins of lymphatic vessels: an historical review

Ribatti D, Crivellato E. Br J Haematol. 2010 Jan 13. [Epub ahead of print] PMID: 20067566

"Summary Work on the lymphatic system began in the 17th century, and by the beginning of the 19th century the anatomy of most of the lymphatic system had been described. One of the most important questions in this field has been the determination of the embryological origin of the lymphatic endothelium. Two theories were proposed. The first suggested that lymphatic endothelium derived by sprouting from venous endothelium, the so-called centrifugal theory. The second, the so-called centripetal theory, suggested that lymphatic endothelium differentiates in situ from primitive mesenchyme, and secondarily acquires connection with the vascular system. More recent evidence has provided support for both hypotheses."


Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature

BMC Dev Biol. 2010 Jun 28;10:72.

Kim H, Nguyen VP, Petrova TV, Cruz M, Alitalo K, Dumont DJ. Sunnybrook Research Institute University of Toronto 2075 Bayview Avenue Toronto, Ontario M4N 3M5, Canada. dan.dumont@sri.utoronto.ca

Abstract

BACKGROUND: In vivo studies demonstrate that the Prox1 transcription factor plays a critical role in the development of the early lymphatic system. Upon Prox1 expression, early lymphatic endothelial cells differentiate from the cardinal vein and begin to express lymphatic markers such as VEGFR-3, LYVE-1 and Podoplanin. Subsequent in vitro studies have found that differentiated vascular endothelial cells can be reprogrammed by Prox1 to express a lymphatic gene profile, suggesting that Prox1 can initiate the expression of a unique gene signature during lymphangiogenesis. While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo.

RESULTS: Overexpression of Prox1 in vascular endothelial cells during embryonic development results in the reprogramming of genes to that of a more lymphatic signature. Consequent to this overexpression, embryos suffer from gross edema that results in embryonic lethality at E13.5. Furthermore, hemorrhaging and anemia is apparent along with clear defects in lymph sac development. Alterations in junctional proteins resulting in an increase in vascular permeability upon Prox1 overexpression may contribute to the complications found during embryonic development.

CONCLUSION: We present a novel mouse model that addresses the importance of Prox1 in early embryonic lymphangiogenesis. It is clear that there needs to be a measured pattern of expression of Prox1 during embryonic development. Furthermore, Prox1 reprograms vascular endothelial cells in vivo by creating a molecular signature to that of a lymphatic endothelial cell.

PMID: 20584329 http://www.ncbi.nlm.nih.gov/pubmed/20584329

http://www.biomedcentral.com/1471-213X/10/72


Tbx1 regulates Vegfr3 and is required for lymphatic vessel development

J Cell Biol. 2010 May 3;189(3):417-24.

Chen L, Mupo A, Huynh T, Cioffi S, Woods M, Jin C, McKeehan W, Thompson-Snipes L, Baldini A, Illingworth E. Program of Cardiovascular Sciences, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Lymphatic dysfunction causes several human diseases, and tumor lymphangiogenesis is implicated in cancer spreading. TBX1 is the major gene for DiGeorge syndrome, which is associated with multiple congenital anomalies. Mutation of Tbx1 in mice recapitulates the human disease phenotype. In this study, we use molecular, cellular, and genetic approaches to show, unexpectedly, that Tbx1 plays a critical role in lymphatic vessel development and regulates the expression of Vegfr3, a gene that is essential for lymphangiogenesis. Tbx1 activates Vegfr3 transcription in endothelial cells (ECs) by binding to an enhancer element in the Vegfr3 gene. Conditional deletion of Tbx1 in ECs causes widespread lymphangiogenesis defects in mouse embryos and perinatal death. Using the mesentery as a model tissue, we show that Tbx1 is not required for lymphatic EC differentiation; rather, it is required for the growth and maintenance of lymphatic vessels. Our findings reveal a novel pathway for the development of the lymphatic vessel network.

PMID: 20439995 http://www.ncbi.nlm.nih.gov/pubmed/20439995

http://jcb.rupress.org/content/189/3/417.long

2009

Lymphatic development

Butler MG, Isogai S, Weinstein BM. Birth Defects Res C Embryo Today. 2009 Sep;87(3):222-31. Review. PMID: 19750516

"The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis and lymphedema. Despite its importance, progress in understanding the origins and early development of this system has been hampered by lack of defining molecular markers and difficulties in observing lymphatic cells in vivo and performing genetic and experimental manipulation of the lymphatic system. Recent identification of new molecular markers, new genes with important functional roles in lymphatic development, and new experimental models for studying lymphangiogenesis has begun to yield important insights into the emergence and assembly of this important tissue. This review focuses on the mechanisms regulating development of the lymphatic vasculature during embryogenesis."

Lymph node lymphangiogenesis: a new concept for modulating tumor metastasis and inflammatory process

Ji RC. Histol Histopathol. 2009 Mar;24(3):377-84. Review. PMID: 19130407

2008

Observations on the prenatal development of human lymphatic vessels with focus on basic structural elements of lymph flow

Lymphat Res Biol. 2008;6(2):89-95.

Petrenko VM, Gashev AA. Department of Human Anatomy, St. Petersburg State Medical Academy, St. Petersburg, Russia.

Abstract

BACKGROUND: The prenatal development of human lymphatic systems has not attracted enough attention by lymphatic researchers in the past. Yet clearly these critical, early events determine the fate and function of the human lymphatic system.

METHODS AND RESULTS: The main focus of these studies was to investigate the embryonic development of human lymphangions including lymphatic valves and muscle cells, to better understand the prenatal formation of basic structural elements of lymph flow. This review in most of its parts is a short summary of the findings. It provides important information necessary for understanding the development and functioning of the human lymphatic system.

CONCLUSIONS: The structural basis of the active lymph transport system--the lymphatic muscle cells and lymphatic valves--which is absolutely necessary for all functions of lymphatic system, is already formed during the first half of the prenatal development in humans. During the second half of this development maturation of this system is already underway. The enlargement of lymphatic muscle cells together with increases in their quantity leads to formation of the multi-layered lymphatic vessel wall, able to develop contractions strong enough to propel lymph downstream of the lymphatic channels against gravity in bipedal humans. The development of the competent valves in lymphatic vessels occurs at the same time creating the ground for effective net, unidirectional lymph flow. The data summarized here represents some of the first systematic studies of the prenatal development of lymphatic muscle cells and valves in humans.

PMID: 18564924 http://www.ncbi.nlm.nih.gov/pubmed/18564924

http://www.liebertonline.com/doi/abs/10.1089/lrb.2008.1001


Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature

Genes Dev. 2007 Oct 1;21(19):2422-32.

Srinivasan RS, Dillard ME, Lagutin OV, Lin FJ, Tsai S, Tsai MJ, Samokhvalov IM, Oliver G. Department of Genetics and Tumor Cell Biology, St. Jude Children's Hospital, Memphis, Tennessee 38105, USA.

Comment in: Lymphat Res Biol. 2007;5(4):275-6.

Abstract

The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP-based lineage-tracing studies using mouse strains expressing Cre recombinase under the control of the Tie2, Runx1, or Prox1 promoter elements. These studies, together with the analysis of Runx1-mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived lymph sacs, lymphatic endothelial cells sprouted, proliferated, and migrated to give rise to the entire lymphatic vasculature, and that hematopoietic cells did not contribute to the developing lymph sacs. We conclude that the mammalian lymphatic system has a solely venous origin. PMID: 17908929

2006

Keystones in lymph node development

J Anat. 2006 Nov;209(5):585-95.

Blum KS, Pabst R. Department of Functional and Applied Anatomy, Hannover Medical School, Germany. blum.katrin@mh-hannover.de

Abstract

New molecular markers are constantly increasing our knowledge of developmental processes. In this review article we have attempted to summarize the keystones of lymphoid tissue development in embryonic and pathological conditions. During embryonic lymph node development in the mouse, cells from the anterior cardinal vein start to bud and sprout, forming a lymph sac at defined sites. The protrusion of mesenchymal tissue into the lymph sacs forms the environment, where so-called 'lymphoid tissue inducer cells' and 'mesenchymal organizer cells' meet and interact. Defects of molecules involved in the recruitment and signalling cascades of these cells lead to primary immunodeficiency diseases. A comparison of molecules involved in the development of secondary lymphoid organs and tertiary lymphoid organs, e.g. in autoimmune diseases, shows that the same molecules are involved in both processes. This has led to the hypothesis that the development of tertiary lymphoid organs is a recapitulation of embryonic lymphoid tissue development at ectopic sites.

PMID: 17062017


1986

The popliteal lymph node of the mouse: internal architecture, vascular distribution and lymphatic supply

J Anat. 1986 Oct;148:25-46.

Kowala MC, Schoefl GI. Department of Experimental Pathology, John Curtin School of Medical Research, Australian National University, Canberra, ACT.

Abstract

The architecture of the mouse popliteal lymph nodes differs from that shown in conventional diagrams. The cortical lymphoid tissue, rather than forming a continuous outer layer, is organised into one or two hemispherical aggregates which project towards the hilus. These aggregates are surrounded by medullary tissue which thus extends to large areas of the surface of the node. The vascular distribution in the lymphoid aggregates is relatively sparse and contrasts with the dense meshwork of capillaries and venules around them. It also contrasts with the high vascularity of medullary tissue. Arterial vessels, especially those of larger calibre, are predominantly seen in the hilar area of the node suggesting that there is extensive branching as the artery enters the node. Capillaries associated with the lymphoid aggregates are usually lined by continuous endothelium, while those in the medulla are generally of the fenestrated type. The microcirculation has an extensive venous capacity and many venous segments are high endothelium venules whose walls are permeated by lymphocytes. Each node receives one or two afferent lymphatic vessels and is drained by up to four or five efferent lymphatic vessels. In approximately half the nodes examined, there were extranodal communications between afferent and efferent lymphatic vessels allowing some lymph to bypass the node. PMID: 3693091

Historic

On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig

Sabin, F. R. (1902).

Am. J. Anat. 1, 367-389.

The lymphatic system in human embryos, with a consideration of the morphology of the system as a whole

Sabin, F. R. (1909).

Am. J. Anat. 9, 43-91.