Development of kidney tubular basement membranes

Although some progress has been made in recent years, there are truly large gaps in our basic knowledge on how the TBM is assembled during development. Some of the new evidence presented here indicates that both the tubular epithelium and interstitial fibroblasts participate in TBM protein biosynthesis during nephrogenesis. In addition, newly assembled segments of TBM are spliced or inserted into existing TBM during tubule expansion and elongation. A similar splicing mechanism has been described previously in the GBM, endocrine organs, and intestinal villi, and this mechanism therefore probably represents a fundamental process of basement membrane formation. A major unresolved question at present, however, is how this mechanism operates at the molecular level. Does the newly formed basement membrane contain identical components as that already present? Since an enzymatic process is likely occurring in the insertion of new matrix into old, which enzymes are involved? What is the cellular origin of these enzymes and which matrix component(s) is their substrate? Even more fundamental yet unanswered questions have to do with the mechanisms of epithelial induction, basement membrane gene activation, and tubular morphogenesis. Once the basement membrane is fully formed at the completion of nephrogenesis, what controls basement membrane turnover and how does this operate? Clearly, much additional research is necessary to address these questions. This work is needed, however, before we can fully understand the important roles basement membranes play in normal development as well as in disease.