Normal and abnormal nephrogenesis.
During the past decade, exciting advances in the fields of cell and molecular biology have provided new insight into the processes of normal and abnormal nephron induction and renal morphogenesis. Although the specific molecular signals that control renal mesenchymal-epithelium inductive interaction remain unknown, recent data suggest that postinductive nephrogenesis may be regulated by the overall balance of a number of local autocrine and/or paracrine growth factor systems. Alterations in the critical balance of regulatory factors might produce a variety of hypoplastic and dysplastic nephropathies or hyperplastic lesions such as tubular cysts. Additional studies demonstrate that extracellular matrix components and cell surface integrins have important regulatory roles in ureteric bud development and branching. Perturbations in matrix or integrin expression due to altered gene activity or toxin exposure would be expected to produce a variety of renal abnormalities ranging from failure of nephron induction (aplasia) to focal disruptions of differentiation (segmental dysplasia). Finally, several groups of genes encoding transcriptional regulatory proteins have been identified that appear to regulate aspects of cell proliferation, pattern formation, and segment-specific differentiation during normal and abnormal nephrogenesis. Future studies will elucidate the roles that specific genes and proteins play in renal development and will ultimately reveal the manner in which their dysregulation or dysfunction causes a variety of developmental renal disorders.
Fouser
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Department of Pediatrics, University of Washington School of Medicine, Seattle.
Avner
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D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology; D005786:Gene Expression Regulation; D016162:Genes, Wilms Tumor; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D007668:Kidney / Q000002:abnormalities / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics
D006133:Growth Substances; D016023:Integrins; D014157:Transcription Factors