The kidney glomerular capillary wall is responsible for the filtration of the blood plasma, and genetic or acquired errors in the composition of this structure can lead to the irretrievable loss of plasma proteins into the urine. The capillary wall itself is unlike any others elsewhere in the body and is comprised of three highly differentiated elements: (1) an inner endothelial cell layer; (2) a basement membrane; and (3) an outer layer of visceral epithelial cells called podocytes. Despite the central importance of the glomerulus in blood filtration, many questions concerning the embryonic derivation of its cellular layers and basement membrane proteins are unanswered. Likewise, little is known about how the capillary normally forms during development, how it is normally maintained in maturity, and what leads to the structural/functional changes that occur in diseases such as diabetes and certain autoimmune disorders.
For the past several years, my laboratory has been investigating the development of the glomerulus during kidney organogenesis, using a variety of molecular genetic, cell and organ culture, immunocytochemical, and transembryonic microsurgical grafting approaches. Specifically, we are currently studying the lineages of glomerular endothelial cells and trying to understand receptor/ligand signals that mediate the differentiation of these cells from angioblasts (endothelial progenitors). In addition, we are exploring the assembly of the glomerular basement membrane, looking at how the different matrix proteins interact with one another in vitro and in the secretory pathway, and how the inventory of these proteins changes as the basement membrane matures. Finally, we are beginning to examine the expression of podocyte-specific proteins during formation of the podocyte foot processes, which are structures that may be the most functionally prominent feature of the filtration barrier.