Faulty Connections Between Circulatory Paths

The parallel circulatory systems of blood and lymph separate during development through the differentiation of blood vessel endothelium. Abtahian et al. (see the Perspective by Jain and Padera) now show that this separation depends on specific intracellular signaling proteins--SLP-76 and Syk--known to be required for correct lymphocyte and platelet function. Abnormal connections between blood and lymphatic vessels occurred in mice lacking either protein and led to severe circulatory defects and hemorrhage. Surprisingly, expression of SLP-76 was not detected on endothelial cells, and abnormal connections occurred in wild-type mice that had been irradiated and received SLP-76-deficient bone marrow. These results suggest that cells of a hematopoietic lineage are required to help coordinate separation of the two vascular systems. F. Abtahian, A. Guerriero, E. Sebzda, M.-M. Lu, R. Zhou, A. Mocsai, E. E. Myers, B. Huang, D. G. Jackson, V. A. Ferrari, V. Tybulewicz, C. A. Lowell, J. J. Lepore, G. A. Koretzky, M. L. Kahn, Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299, 247-251 (2003). [Abstract] [Full Text] R. K. Jain, T. P. Padera, Lymphatics make the break. Science 299, 209-210 (2003). [Summary] [Full Text]