Histochemistry and Cell Biology

, Volume 135, Issue 6, pp 603–613

Dysmorphogenesis of lymph nodes in Foxc2 haploinsufficient mice

  • Hiroshi Shimoda
  • Michael J. Bernas
  • Marlys H. Witte
Original Paper

DOI: 10.1007/s00418-011-0819-x

Cite this article as:
Shimoda, H., Bernas, M.J. & Witte, M.H. Histochem Cell Biol (2011) 135: 603. doi:10.1007/s00418-011-0819-x

Abstract

Dysmorphogenesis of lymph nodes displayed in a fork head transcription factor Foxc2 haploinsufficient mice—a model for lymphedema-distichiasis syndrome—was studied by immunohistochemistry and electron microscopy. The Foxc2 heterozygous mice manifested lymph node hyperplasia composed of conspicuous proliferation of endothelial cells forming the lymphatic sinus and α-smooth muscle actin (SMA)-immunopositive fibroblast-like cells in the lymphatic pulp, particularly around the sinus. The hyperplastic sinus endothelial cells and the SMA-positive cells demonstrated distinct immunolocalization of platelet-derived growth factor (PDGF)-B, a crucial chemoattractant for vascular mural cell recruitment, and its receptor, PDGFR-β, respectively. The observations suggest that the sinus endothelial cells elicit abnormal recruitment of the fibroblast-like cells as a type of vascular mural cells via PDGF-B/PDGFR-β signaling in lymph nodes of the Foxc2 heterozygotes. Furthermore, in Foxc2 heterozygous lymph nodes, recruited SMA-positive cells displayed an intense immunoreaction for vascular endothelial growth factor (VEGF)-C, a highly specific lymphangiogenic factor, and its receptor, VEGFR-3, was preferentially distributed in the lymphatic sinus endothelial cells. These findings suggest that an interactive cycle between lymphatic sinus endothelial cells and the fibroblast-like cells, which involves PDGF-B/PDGFR-β and VEGF-C/VEGFR-3 signaling, is essential for aberrant hyperplasia of the lymphatic sinus and the fibroblast-like cells in Foxc2 haploinsufficiency.

Keywords

Foxc2 haploinsufficiencyLymph nodeImmunohistochemistryMouse

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hiroshi Shimoda
    • 1
    • 2
    • 3
  • Michael J. Bernas
    • 1
  • Marlys H. Witte
    • 1
  1. 1.Department of SurgeryThe University of ArizonaTucsonUSA
  2. 2.Department of Human Anatomy, Faculty of MedicineOita UniversityOitaJapan
  3. 3.Human Biology, Department of Health SciencesOita University of Nursing and Health SciencesOitaJapan