Early organogenesis of the kidney

The early organogenesis of the kidney, is a complicated, multi-step process that begins with the development of the ureter. The ureter development is regulated by the surrounding mesenchyme and growth factors which allows the ureter tree structure to branch and proliferate. This ureter growth triggers the endothelialization and morphogenesis of the mesenchyme. The mesenchymal cells will thus differentiate into several types of endothelial cells which will line the endothelium of the kidney, and the mesenchymal cells will undergo morphogenic changes. These two processes propagate each other, as endothelial-mesenchymal cell interaction is a closely intertwined process. The morphological change of the mesenchymal cells starts with loose mesenchyme. This is intertwined with the development and branching of the ureter. The ECM of the mesenchyme changes in composition such that it experiences an increase in several epithelial-type proteins, collagen IV and V, laminin, heparin sulphate proteoglycan, and entactin. DNA synthesis then significantly increases within the mesenchyme. The resulting condensate of cells thus experience increased adhesive capabilities and decreased motility. Most of this condensate ends up gathering at the periphery of the aggregate and serves as a scaffold for the rest of the cells throughout the organogenesis process.

Concurrently, the mesenchymal cells acquire and epithelial, elongated shape within the aggregate. Two slits open within this aggregate, creating the S-shape structure of the early nephron. Endothelial cells migrate into the crevice of the S-shape body and begin the vascularization process. The origin of these endothelial cells is not well understood. Epithelial podocytes and these vascular endothelial cells then contribute to the formation of the glomerular basement membrane, or GBM. Capillary cells from outside then migrate in to the crevice to complete the vascularization process, using the increased concentration of stromal fibronectin to home into the correct location. The key to all of these steps is the formation of the ureter, which serves as an inductor for the rest of the organogensis process. This paper described how without the ureter development, the development of the kidney did not proceed. This chain of events of is still molecular unexplained and some elements are not well understood, but the importance of ureter development is well-established.

The process described in this paper would be essential in any project to engineer an artificial kidney or parts of a kidney. Of interest is the foremost importance of the introduction of the ureter to the whole process. In any method to develop an artificial kidney, the first step would be to introduce a developing ureter structure. This ureter will likely have to be derived from another organism rather than engineered, because the ureter contains within it the “programming” for branching and growth which is not well understood and difficult to emulate in vitro. The introduction of this ureter structure, in theory, should organize and facilitate the remaining development of the organ.