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Free Content The Current Concepts of the Embryology of the Lymphatic System

The overall lymphatic system is the major factor in maintaining the integrity of our cellular immunity as well as in playing a role in lipid metabolism and hormone transport. There is a major interest in the ability of certain tumors to induce lymphangiogenesis and the potential impact that this may have on treatment. The lymph nodes also play a significant role as prognosticators of survival in cancer patients, and, the more complete our knowledge of this critical system, the better one can appreciate its complexity and function. The best place to start is with the origin of the lymphatic vasculature. In the head and neck, this vascular network arises primarily from the anterior cardinal veins as well as from the intersomitic veins and the superficial venous plexus. Thus, to fully understand lymphangiogenesis, it is necessary to briefly review vasculogenesis and angiogenesis to appreciate how these vessels arise. This review examined the current concepts of the development first of the vascular system and then of the lymphatic system. The review was highly illustrated to assist the reader in understanding the embryology. There also was a brief section noting the congenital abnormalities that may arise when the embryology goes awry.

Learning Objective: To understand how the lymphatic system develops and what can go wrong when it does not develop normally.

Keywords: ALK-1 = activin receptor-like kinase 1; ANG = angiopoietin; CCBE1 = collagen and calcium binding protein; CCL = lymphoid chemokine; CCR7 = lymphoid chemokine 7; CD = cluster of differentiation molecule; CDC42 = cell division control protein 42; CER7 = arabidopsis thaliana gene 7; CLEC-2 = A receptor on platelets; COUP-TFII = COUP (chicken ovalbumin upstream promoter) transcription factor 2; CXCL = lymphoid chemokine (C-X-C motif chemokine also known as B lymphocyte chemoattractant protein); CXCR5 = lymphoid chemokine receptor; CYP26B1 = a gene encoding a member of the cytochrome P450 superfamily; ClES-2 = COUP transcription factor two also known as NR2F2 (nuclear receptor subfamily 2, group F, member 2); Dll4 = delta-like 4; ECM = extracellular matrix; EMILIN-1 = an elastic microfibule-associated protein found in the ECM; EPH = belongs to the subfamily of protein-tyrosine kinase family and serves as ligands for the ephrin receptor; Ephrin = receptor for EPH; FIAF = fasting-induced adipose factor; FN-E111A = fibronectin protein; FOXC2 = Forkhead box protein C2; GATA = globin transcription factor 1; GJC2 = gap junction protein 2; HEV = high endothelial venule; HGF = hepatocyte growth factor; HIF-1 = hypoxia inducible factor; ICAM1+ = intercellular adhesion molecule; ID2 = the negative regulator of basic helix-loop-helix protein signaling; IL = interleukin; Integrin a5b1 = mediates cell adhesion and migration on fibronectin; KRAS = Kirsten rat sarcoma gene; LEC = lymphatic endothelial cell; LT = lymphotoxin (α and β); LTi = lymphoid tissue inducer; LVC = lymphatic valve-forming cell; LYVE-1 = A transmembrane receptor for glycosaminoglycan hyaluronan; MC = mesenchymal organizer cell; MET = receptor for HGF; MMP = matrix metalloproteinase; NEMO NF-kappa-B essential modulator gene; NFATC1 = nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent-1; NKRAS = homolog of KRAS; NOTCH = NOTCH signaling is required in regulating cell polarity and cell-cell communication; NRP = neuropilin; P13K = phosphoinositde 3-kinase; PDGF = platelet-derived growth factor; PECAM-1 = platelet/endothelial cell adhesion molecule 1; PLCγ2 = phospholipase C gamma 2 protein; PROX-1 = prospero-related homeobox-1; PTPN14,11 = protein phosphatase nonreceptor type 14, 11; Podoplanin = a mucin-type glycoprotein expressed on lymphatic endothelial cells; RA = retinoic acid; RAC1 = also known as Ras-related C3l; RΟγt = orphan nuclear hormone receptor; SLC = human solute carrier; SLP = adapter protein involved in signal transduction cascade; SLP6SH2 = SLP76SH2 domain containing leukocyte protein of 76kDa; SOS1 = son of sevenless homolog 1; SOX = sex determining region Y-box transcription factor; SYK = spleen tyrosine kinase protein or Helsingin Suomalainen Yhteiskoulu molecule: tyrosine kinase; TGFβ = transforming growth factor β; TIE = tyrosine kinase receptor; TRANCE = THF-related activation-induced cytokine; VCAM = vascular cell adhesion molecule; VEGF = vascular endothelial growth factor; mRNA = messenger RNA chain; myocardin A smooth muscle‐specific transcriptional coactivator of serum response factor; α9 = neuronal acetylcholine receptor subunit

Document Type: Research Article

Publication date: April 1, 2017

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