Cardiovascular System - Lymphatic Development
|Embryology - 22 Oct 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Lymphatic Vessels
- 4 Lymphatic Vessel Development
- 5 Lymphatic Vessel Contraction
- 6 Molecular Development
- 7 Abnormalities
- 8 References
- 9 Additional Images
- 10 External Links
- 11 Glossary Links
An important part of the cardiovascular system is the lymphatic vasculature, which functions to both return interstitial fluid (lymph) to the bloodstream and also as part of the immune system. In the embryo, lymphatic development begins at the cardinal vein, where venous endothelial cells differentiate (express Prox1) to form lymphatic endothelial cells that out-pocket and bud to form lymph sacs. During development these lymph sacs remodel to form both the lymphatic space within future nodes, formed by engulfed connective tissue, and the associated afferent and efferent vessel network.
This system was first identified by Aselli G. (1627) in a paper "De Lacteibus sive Lacteis Venis", Quarto Vasorum Mesarai corum Genere novo invento. Milan: Mediolani. Then postulated by Sabin (1902) as venous in origin, it required a recent 2007 lineage tracing study to confirm this theory. Only vertebrates possess a true lymphatic vascular system, with primitive fish possessing a lymphatic-like secondary vascular system that also contains blood. Clinically, important for roles in immune surveillance and oncogenic (cancer) processes.
|Cardiovascular Links: Introduction | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | Heart | Coronary Circulation | Heart Valve | Heart Rate | Circulation | Blood | Blood Vessel | Blood Vessel Histology | Cardiac Muscle Histology | Lymphatic | Ductus Venosus | Spleen | Stage 22 | Abnormalities | OMIM | 2012 ECHO Meeting | 2016 Cardiac Review | Category:Cardiovascular|
Some Recent Findings
- Lymph capillaries - begin as blind-ending tubes in connective tissue, larger than blood capillaries, very irregularly shaped.
- Lymph collecting vessels - larger and form valves, morphology similar to lymph capillaries.
- Lymph ducts - 1 or 2 layers of smooth muscle cells in wall.
- (Remember the anatomy acronym NAVL = Nerve, Artery, Vein and Lymph)
- single-cell layer of overlapping endothelial cells
- lack a basement membrane
- lack smooth muscle cells or pericytes (pre-collecting and collecting trunks contain both)
- linked by discontinuous endothelial cell-cell junctions (button-like).
- junctions open in response to increased interstitial fluid pressure.
Lymphatic microvasculature model
Lymphatic Vessel Development
Tunneling model of lymphatic vessel formation.
|The model shown here is from a recent paper and is based on ultrastructural observations performed in in vitro and in vivo models of lymphangiogenesis. Lymphatic endothelial cells (LEC) display tight junctions and interdigitations, and are connected to the surrounding collagen fibers by anchoring filaments.
Note that this postnatal model may differ from developmental lymphatic vessel development.
Lymphatic Vessel Contraction
Lymphatic vessels undergo spontaneous rhythmic contractions which aid lymph flow. This is most easily demonstrated in models based upon mesentry lymphatics of the gastrointestinal tract. Contractile activity is regulated by physical factors (transmural pressure) and neurological (alpha-adrenergic, histamine, bradykinin) acting on lymphatic smooth muscle. Contractility and receptor expression may also be different in different parts of the lymphatic system.
Alpha-adrenergic - alpha 1- and not alpha 2-adrenoceptors.
Histamine - lymphatic smooth muscle via stimulation of H(1) (and in some vessels H(2)) receptors.
Bradykinin - chronotropic but not inotropic effects on lymphatic pump activity via stimulation of B1 receptors.
Lymphatic Vasculature Organization
Notch probably mediates choice of fate between arterial and venous.
Prox1 Prospero-related Homeobox 1 - expressed in a subpopulation of blood endothelial cells that then generate, by both budding and sprouting, cells of the lymphatic vascular system. Triggers the molecular program leading to the formation of the lymphatic system. (OMIM - PROSPERO-RELATED HOMEOBOX 1; PROX1)
Tie (Tie1 and Tie2) tyrosine kinase receptors.
Vascular endothelial growth factor (VEGF) family of proteins and angiopoietin/Tie, Notch, and ephrin/Eph pathways play major roles in eary vessel development. (VEGFR-3)
Dysplasia of childhood form lymphatic capillaries or collectors, which form fluid-filled cysts.
- lymphatic spaces lined by endothelium
- smooth muscle fascicles in the septa between the lymphatic spaces
- lymphoid aggregates in the delicate collagenous stroma
- Sabin, F. R. On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig. (1902) Am. J. Anat. 1, 367-389.
- R Sathish Srinivasan, Miriam E Dillard, Oleg V Lagutin, Fu-Jung Lin, Sophia Tsai, Ming-Jer Tsai, Igor M Samokhvalov, Guillermo Oliver Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes Dev.: 2007, 21(19);2422-32 PubMed 17908929
- Ying Yang, Guillermo Oliver Development of the mammalian lymphatic vasculature. J. Clin. Invest.: 2014, 124(3);888-97 PubMed 24590273
- Luca Del Giacco, Anna Pistocchi, Anna Ghilardi prox1b Activity is essential in zebrafish lymphangiogenesis. PLoS ONE: 2010, 5(10);e13170 PubMed 20976189
- Guillermo Oliver, Kari Alitalo The lymphatic vasculature: recent progress and paradigms. Annu. Rev. Cell Dev. Biol.: 2005, 21;457-83 PubMed 16212503
- Michael S Pepper, Mihaela Skobe Lymphatic endothelium: morphological, molecular and functional properties. J. Cell Biol.: 2003, 163(2);209-13 PubMed 14581448 | JCB
- 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.
- Stefan Schulte-Merker, Amélie Sabine, Tatiana V Petrova Lymphatic vascular morphogenesis in development, physiology, and disease. J. Cell Biol.: 2011, 193(4);607-18 PubMed 21576390 | PMC3166860 | J Cell Biol.
- Lymphology - Journal Homepage
Guillermo Oliver, R Sathish Srinivasan Lymphatic vasculature development: current concepts. Ann. N. Y. Acad. Sci.: 2008, 1131;75-81 PubMed 18519960
C Bellini, F Boccardo, E Bonioli, C Campisi Lymphodynamics in the fetus and newborn. Lymphology: 2006, 39(3);110-7 PubMed 17036631
Guillermo Oliver, Kari Alitalo The lymphatic vasculature: recent progress and paradigms. Annu. Rev. Cell Dev. Biol.: 2005, 21;457-83 PubMed 16212503
Meiko Takahashi, Takanobu Yoshimoto, Hajime Kubo Molecular mechanisms of lymphangiogenesis. Int. J. Hematol.: 2004, 80(1);29-34 PubMed 15293565
Guillermo Oliver Lymphatic vasculature development. Nat. Rev. Immunol.: 2004, 4(1);35-45 PubMed 14704766
Guillermom Oliver, Natasha Harvey A stepwise model of the development of lymphatic vasculature. Ann. N. Y. Acad. Sci.: 2002, 979;159-65; discussion 188-96 PubMed 12543725
Nicole C Johnson, Miriam E Dillard, Peter Baluk, Donald M McDonald, Natasha L Harvey, Sharon L Frase, Guillermo Oliver Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes Dev.: 2008, 22(23);3282-91 PubMed 19056883
R Sathish Srinivasan, Miriam E Dillard, Oleg V Lagutin, Fu-Jung Lin, Sophia Tsai, Ming-Jer Tsai, Igor M Samokhvalov, Guillermo Oliver Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes Dev.: 2007, 21(19);2422-32 PubMed 17908929
Fredrik Bäckhed, Peter A Crawford, David O'Donnell, Jeffrey I Gordon Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc. Natl. Acad. Sci. U.S.A.: 2007, 104(2);606-11 PubMed 17202268
Jay W Shin, Michael Min, Fréderic Larrieu-Lahargue, Xavier Canron, Rainer Kunstfeld, Lynh Nguyen, Janet E Henderson, Andreas Bikfalvi, Michael Detmar, Young-Kwon Hong Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis. Mol. Biol. Cell: 2006, 17(2);576-84 PubMed 16291864
Terhi Karpanen, Maria Wirzenius, Taija Mäkinen, Tanja Veikkola, Hidde J Haisma, Marc G Achen, Steven A Stacker, Bronislaw Pytowski, Seppo Ylä-Herttuala, Kari Alitalo Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am. J. Pathol.: 2006, 169(2);708-18 PubMed 16877368
Guillermo Oliver, Michael Detmar The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature. Genes Dev.: 2002, 16(7);773-83 PubMed 11937485
Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity Nicole C. Johnson, Miriam E. Dillard, Peter Baluk, Donald M. McDonald, Natasha L. Harvey, Sharon L. Frase, and Guillermo Oliver Genes Dev. 2008;22 3282-3291
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Cite this page: Hill, M.A. 2017 Embryology Cardiovascular System - Lymphatic Development. Retrieved October 22, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Lymphatic_Development
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