Molecular Trigger Initiates Embryonic Lymph System Divergence

A recent study has found that the SLP-76 and Syk proteins, known to have signaling functions in white blood cell development, are critical factors in the process that separates the lymphatic system from the circulatory system during development. The finding was reported in the January 10, 2003, issue of Science.
At a certain point in fetal development, cells from the newly emerged blood circulatory system diverge and form the vessels of the lymphatic system. The mechanism of this divergence has not been well studied.

In the current report, investigators from the University of Pennsylvania School of Medicine (Philadelphia, USA; www.upenn.edu) genetically engineered lines of mice lacking the SLP-76 or Syk proteins. They found that most animals lacking SLP-76 had severe abnormalities in white blood cell development. Additionally, animals that grew to adulthood had larger than normal hearts. Blood was being forced into the lymphatic system, and their hearts were larger because the lymphatic channels mediated arterio-venous shunting of blood.

In SLP-76 deficient animals, the vascular and lymphatic systems never separated during fetal development. Similar effects were found in animals lacking Syk. "It is becoming increasingly clear that the regulation of signal transduction is critical for understanding both basic biological processes and the diseases that occur as these processes go awry,” explained corresponding author Dr. Mark Koretzky, professor in the University of Pennsylvania's department of pathology and laboratory medicine. "Only now are we really beginning to understand the clinical potential these molecular signals may have in fighting disease.”




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