title: Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.
abstract: In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Morello
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002454:Cell Differentiation; D022081:Cell Surface Extensions / Q000502:physiology / Q000648:ultrastructure; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology* / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D008954:Models, Biological; D009261:Nail-Patella Syndrome / Q000235:genetics / Q000473:pathology*; D009404:Nephrotic Syndrome / Q000235:genetics / Q000473:pathology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D015027:Zebrafish
chemical_list: D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D003094:Collagen