ZFIN ID: ZDB-PUB-100621-24
Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies
Flores, M.V., Hall, C.J., Crosier, K.E., and Crosier, P.S.
Date: 2010
Source: Developmental dynamics : an official publication of the American Association of Anatomists   239(7): 2128-2135 (Journal)
Registered Authors: Crosier, Kathy, Crosier, Phil, Flores, Maria, Hall, Chris
Keywords: lymphangiogenesis, drug discovery, lyve1, rapamycin, Zebrafish
MeSH Terms:
  • Animals
  • In Situ Hybridization
  • Lymphangiogenesis/drug effects
  • Lymphangiogenesis/genetics
  • Lymphangiogenesis/physiology*
  • Mice
  • Neoplasms/pathology*
  • Sirolimus/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 20549745 Full text @ Dev. Dyn.
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ABSTRACT
Lymphangiogenesis induced during tumor growth contributes to metastasis. Genetic and chemical screens using the zebrafish model have the potential to enhance our understanding of lymphangiogenesis, and lead to the discovery of pharmacological agents with activity in the lymphatic system. Large-scale screening of lymphatic development in the whole zebrafish embryo requires a specific lymphatic endothelial cell marker. We isolated the zebrafish ortholog of Lyve1, and analyzed its expression pattern during embryogenesis, and under conditions where key regulators of lymphangiogenesis such as Prox1 and VegfC were depleted. Like humans, zebrafish embryos form lymph sacs, lymphangioblasts arise from venous endothelia, and they form asymmetric left and right collecting ducts. By monitoring the earliest lymphatic sprouting in the head, a pilot drug assay was performed showing rapamycin, an inhibitor of mammalian lymphangiogenesis, can also suppress zebrafish lymphangiogenesis. This work opens up a novel opportunity to further the understanding of, and potentially manipulate, human lymphangiogenesis.
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