UP-REGULATION OF THE CONNEXIN43(-TISSUE BEFORE THE GROWTH OF STEM-CELLS() GAP JUNCTION NETWORK IN HEMATOPOIETIC)

The early developmental stages of haemopoiesis are thought to be regul ated by paracrine growth factors and by the haemopoietic environment. Are gap junctions involved here? Gap junctions are structures in cell membranes allowing the direct transfer of ions and small molecules bet ween adjacent cells and are known to be involved in development. We ha ve found that although connexin-43 gap junctions are rare, (0.00016+/- 0.0002/mu m(2) tissue) in normal adult mouse marrow their expression i s 80-fold higher (0.0292+/-0.0147/mu m(2)) in neonatal marrow. One dif ference between neonatal and adult haemopoietic tissue is that in the latter more haemopoietic cells are dividing. To test if more gap junct ions were due to increased division we altered adult blood-formation b y mobilizing or destroying end cells - granulocytes and red cells - or by forcing stem cells to divide by making them regenerate an ablated blood-forming system. Mobilizing end cells had no effect on the number or distribution of gap junctions in marrow but forced stem cell divis ion caused a 100-fold increase in gap junction expression and did so b efore any recognizable haemopoietic cells formed. There were greater t han normal numbers of gap junctions in radio-protected adult mouse mar row. The cells coupled by gap junctions are TE-7(+) mesodermally deriv ed fibroblasts, STRO-1(+) stromal cells, and CD45(+) and CD34(+) haemo poietic cells. We propose that there is a latent network of Cx43(+) ga p junctions in normal quiescent marrow. In response to events that cal l for active division of stem cells this network is amplified and coup led to haemopoietic stem cells, perhaps enabling them to divide.