An important part of the cardiovascular system is the lymphatic vasculature, which functions to return interstitial fluid (lymph) to the bloodstream. 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 |
(Image: US National Cancer Institute) |
Page Links: Introduction | Reading | Development Overview | Vessels | Lymphatic Vessel Contraction | Molecular Development | Abnormalities | WWW Links | References | Glossary | Terms
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
"...blood endothelial cells (BECs) identity and promotes and maintains lymphatic endothelial cell (LEC) identity; switching off Prox1 activity is sufficient to initiate a reprogramming cascade leading to the dedifferentiation of LECs into BECs. Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity."
Lymphatic vasculature development: current concepts. Oliver G, Srinivasan RS. Ann N Y Acad Sci. 2008;1131:75-81. Review.
Backhed F, Crawford PA, O'Donnell D, Gordon JI. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):606-11.
Yaniv K, Isogai S, Castranova D, Dye L, Hitomi J, Weinstein BM. Live imaging of lymphatic development in the zebrafish. Nat Med. 2006 Jun;12(6):711-6.
"Our results show lymphatic endothelial cells of the thoracic duct arise from primitive veins through a novel and unexpected pathway."
Bellini C, Boccardo F, Bonioli E, Campisi C. Lymphodynamics in the fetus and newborn. Lymphology. 2006 Sep;39(3):110-7.
"The purpose of this review is to discuss the complex mechanism that regulates volume in the fetus and newborn as well as the regulation of fluid distribution between the plasma and interstitial fluid, while placing special emphasis on the role the lymphatic system plays in mediating and maintaining this distribution."
(More? References)
Model of lymphatic vessel development in the mouse. (Original image see Oliver G, Alitalo K.)
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.
Angiopoietins (Ang1–Ang4)
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. (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.
Lymphangioma - dysplasia of childhood form lymphatic capillaries or collectors, which form fluid-filled cysts.
International Society of Lymphology ISL | Lymphology Journal
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Reviews
Lymphatic vasculature development: current concepts. Oliver G, Srinivasan RS. Ann N Y Acad Sci. 2008;1131:75-81. Review.
Bellini C, Boccardo F, Bonioli E, Campisi C. Lymphodynamics in the fetus and newborn. Lymphology. 2006 Sep;39(3):110-7.
Cueni LN, Detmar M. New insights into the molecular control of the lymphatic vascular system and its role in disease. J Invest Dermatol. 2006 Oct;126(10):2167-77.
Oliver G, Alitalo K. The Lymphatic Vasculature: Recent Progress and Paradigms. Annu Rev Cell Dev Biol. 2005 Nov 10;21:457-483.
Takahashi M, Yoshimoto T, Kubo H. Molecular mechanisms of lymphangiogenesis. Int J Hematol. 2004 Jul;80(1):29-34.
Oliver G. Lymphatic vasculature development. Nat Rev Immunol. 2004 Jan;4(1):35-45.
Oliver G, Harvey N. A stepwise model of the development of lymphatic vasculature. Ann N Y Acad Sci. 2002 Dec;979:159-65; discussion 188-96.
Articles
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
Backhed F, Crawford PA, O'Donnell D, Gordon JI. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):606-11.
Shin JW, Min M, Larrieu-Lahargue F, Canron X, Kunstfeld R, Nguyen L, Henderson JE, Bikfalvi A, Detmar M, Hong YK. 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 Feb;17(2):576-84.
Karpanen T, Wirzenius M, Makinen T, Veikkola T, Haisma HJ, Achen MG, Stacker SA, Pytowski B, Yla-Herttuala S, Alitalo K. Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am J Pathol. 2006 Aug;169(2):708-18. PMID: 16877368 [PubMed - indexed for MEDLINE]
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Lymphatics? This is a hard one because while much has been written about cardiovascular development and the heart, very little information was ever included on lymphatic development. This page includes links to some recent reviews which should begin to rectify this situation.
Please email Dr Mark Hill if you wish to make a comment about this current project.
