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Maldevelopment of dermal lymphatics in Wnt5a-knockout-mice
- Source :
- Developmental Biology. 381(2):365-376
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Maintenance of tissue homeostasis and immune surveillance are important functions of the lymphatic vascular system. Lymphatic vessels are lined by lymphatic endothelial cells (LECs). By gene micro-array expression studies we recently compared human lymphangioma-derived LECs with umbilical vein endothelial cells (HUVECs). Here, we followed up on these studies. Besides well-known LEC markers, we observed regulation of molecules involved in immune regulation, acetylcholine degradation and platelet regulation. Moreover we identified differentially expressed WNT pathway components, which play important roles in the morphogenesis of various organs, including the blood vascular system. WNT signaling has not yet been addressed in lymphangiogenesis. We found high expression of FZD3, FZD5 and DKK2 mRNA in HUVECs, and WNT5A in LECs. The latter was verified in normal skin-derived LECs. With immunohistological methods we detected WNT5A in LECs, as well as ROR1, ROR2 and RYK in both LECs and HUVECs. In the human, mutations of WNT5A or its receptor ROR2 cause the Robinow syndrome. These patients show multiple developmental defects including the cardio-vascular system. We studied Wnt5a-knockout (ko) mouse embryos at day 18.5. We show that the number of dermal lymphatic capillaries is significantly lower in Wnt5a-null-mice. However, the mean size of individual lymphatics and the LEC number per vessel are greater. In sum, the total area covered by lymphatics and the total number of LECs are not significantly altered. The reduced number of lymphatic capillaries indicates a sprouting defect rather than a proliferation defect in the dermis of Wnt5a-ko-mice, and identifies Wnt5a as a regulator of lymphangiogenesis.
- Subjects :
- Male
FABP4
Mice
ENTPD1
LGALS3BP
Lymphangiogenesis
Wnt Signaling Pathway
ROR1
Tissue homeostasis
Cells, Cultured
Skin
Mice, Knockout
Wnt signaling pathway
Cell biology
WNT5A
Lymphatic Endothelium
medicine.anatomical_structure
Lymphatic system
Knockout mouse
embryonic structures
Intercellular Signaling Peptides and Proteins
government.form_of_government
Biology
Receptor Tyrosine Kinase-like Orphan Receptors
Wnt-5a Protein
FDZ3
Dermis
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Lymphatic endothelial cell
Molecular Biology
Cell Proliferation
Lymphatic Vessels
RYK
Lymphangioma
DKK2
fungi
Infant
Cell Biology
Embryo, Mammalian
Frizzled Receptors
Wnt Proteins
body regions
Case-Control Studies
Immunology
Mutation
government
AChE
sense organs
Transcriptome
Biomarkers
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 381
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....b0b5f8007e987be2128952b3196944b7
- Full Text :
- https://doi.org/10.1016/j.ydbio.2013.06.028