Lymphatic fate specification: an ERK-controlled transcriptional program

Microvasc Res. 2014 Nov;96:10-5. doi: 10.1016/j.mvr.2014.07.016. Epub 2014 Aug 15.


Lymphatic vessels are intimately involved in the regulation of water and solute homeostasis by returning interstitial fluid back to the venous circulation and play an equally important role in immune responses by providing avenues for immune cell transport. Defects in the lymphatic vasculature result in a number of pathological conditions, including lymphedema and lymphangiectasia. Knowledge of molecular mechanisms underlying lymphatic development and maintenance is therefore critical for understanding, prevention and treatment of lymphatic circulation-related diseases. Research in the past two decades has uncovered several key transcriptional factors (Prox1, Sox18 and Coup-TFII) controlling lymphatic fate specification. Most recently, ERK signaling has emerged as a critical regulator of this transcriptional program. This review summarizes our current understanding of lymphatic fate determination and its transcriptional controls.

Keywords: ERK; Lymphangiogenesis; Lymphatic fate; Prox1; Sox18; VEGF-C.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Lineage
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • Lymphangiogenesis / physiology*
  • Lymphatic Vessels / physiology*
  • Mice
  • Models, Biological
  • Receptors, Notch / metabolism
  • SOXF Transcription Factors / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • Tumor Suppressor Proteins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Homeodomain Proteins
  • Receptors, Notch
  • SOXF Transcription Factors
  • Sox18 protein, mouse
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor A
  • prospero-related homeobox 1 protein
  • Extracellular Signal-Regulated MAP Kinases