Regulatory pathways in blood-forming tissue with particular reference to gap junctional communication.

Blood formation by pluripotent stem cells and their progeny is thought to be regulated by receptor-ligand interactions between cell-substrate, cell-cell and cell-matrix in the bone marrow. Primitive stem cells form progenitors and, in their turn, these give rise to haemopoietic progeny which are more specifically committed in that they can form progressively fewer types of blood cells. Recently we have established that direct cell-cell communication via gap junctions may be part of this regulatory system. Connexin43 gap junctions metabolically couple the three dimensional meshwork of bone marrow stromal cells to form a functional syncytium in which some blood-forming cells are also coupled. The expression of gap junctions in the bone marrow is markedly upregulated when there is an urgent and substantial demand for blood-formation; for example, following cytotoxic injury after 5-fluorouracil or irradiation; or during neonatal blood-formation and in the epiphysis of growing bones. Chemical blockade of gap junctions blocks blood-formation in long-term cultures but is reversible after the blockade has been relieved. This short review highlights briefly the known regulatory mechanisms of blood-formation with especial attention to gap junctional communication.