Regulation of hematopoiesis by gap junction-mediated intercellular communication

Gap junctions are intercellular channels formed by individual structural un its known as connexins (Cx) that allow the intercellular exchange of small molecules between cells. The presence of Cx protein in bone marrow and thym ic stromal cells and the demonstration that these cells are functionally co upled have led to the hypothesis that groups of stromal cells in the bone m arrow and thymus form a functional syncytium through which their hematopoie tic support capacity is coordinated. The validity of this hypothesis was re cently tested in a newly developed strain of mice in which the gene encodin g Cx43, the principal Cx expressed in hematopoietic tissues, was disrupted. Studies of myelopoiesis and lymphopoiesis in these Cx43-deficient mice rev ealed that expression of Cx43 in the bone marrow and thymus is critically i mportant during periods of active hematopoiesis, such as during embryogenes is and after recovery from cytoablative treatments. The clinical implicatio ns of these observations, as well as issues that remain to be addressed to understand the mechanism(s) by which gap junctions regulate hematopoiesis, are addressed.