PUBLICATION
prox1b Activity Is Essential in Zebrafish Lymphangiogenesis
- Authors
- Del Giacco, L., Pistocchi, A., and Ghilardi, A.
- ID
- ZDB-PUB-101027-48
- Date
- 2010
- Source
- PLoS One 5(10): e13170 (Journal)
- Registered Authors
- Del Giacco, Luca, Ghilardi, Anna
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Base Sequence
- DNA Primers
- Evolution, Molecular
- Homeodomain Proteins/genetics*
- In Situ Hybridization
- Lymphangiogenesis/genetics*
- Molecular Sequence Data
- Tumor Suppressor Proteins/genetics*
- Zebrafish/genetics*
- PubMed
- 20976189 Full text @ PLoS One
Citation
Del Giacco, L., Pistocchi, A., and Ghilardi, A. (2010) prox1b Activity Is Essential in Zebrafish Lymphangiogenesis. PLoS One. 5(10):e13170.
Abstract
BACKGROUND: The lymphatic vascular system, draining interstitial fluids from most tissues and organs, exerts crucial functions in several physiological and pathological processes. Lymphatic system development depends on Prox1, the first marker to be expressed in the endothelial cells of the cardinal vein from where lymph vessels originate. Prox1 ortholog in the optically clear, easily manipulated zebrafish model has been previously isolated and its contribution to lymphangiogenesis has been clarified. Because of a round of genome duplication occurred at the base of teleosts radiation, several zebrafish genes have been retained in duplicate through evolution. We investigated for the presence of additional prox1 genes and determined their role in zebrafish lymphangiogenesis.
METHODOLOGY/PRINCIPAL FINDINGS: We isolated a second ortholog, named prox1b, and analyzed its expression during development by whole mount in situ hybridization (WISH). We detected strong prox1b expression in the endothelium of the posterior cardinal vein (PCV) from where lymphatic precursors originate. To analyze prox1b involvement in lymphangiogenesis we utilized the fli1:GFP transgenics and followed the formation of the toracic duct (TD), the primary lymph vessel in fish, after prox1b knockdown. Our findings clearly demonstrated that the absence of prox1b activity severely hampers the formation of the TD.
CONCLUSIONS/SIGNIFICANCE: This work provides substantial progress toward the understanding of zebrafish lymphangiogenesis. In light of the features shared by the lymphatic systems of zebrafish and higher vertebrates, the establishment of such lymphatic model will provide a powerful tool to study, for instance, disorders of body fluid homeostasis, inflammation and cancer metastasis, and may ultimately contribute to novel therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping