FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons
| Autor: | Doris Herzlinger, Cristina Cebrián, Erik N. Meyers, Uta Grieshammer, Gail R. Martin, Roger M. Ilagan |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Mesoderm Fibroblast Growth Factor 8 Cell Survival Mice Transgenic Nephron Biology Kidney morphogenesis Mice FGF8 Internal medicine WNT4 medicine Animals Progenitor cell Molecular Biology Alleles urogenital system Mesenchymal stem cell Gene Expression Regulation Developmental Nephrons Cell biology Fibroblast Growth Factors Phenotype Endocrinology medicine.anatomical_structure Spinal Cord Collecting duct system Signal Transduction Developmental Biology |
| Zdroj: | Development. 132:3847-3857 |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.01944 |
| Popis: | During kidney morphogenesis, the formation of nephrons begins when mesenchymal nephron progenitor cells aggregate and transform into epithelial vesicles that elongate and assume an S-shape. Cells in different regions of the S-shaped body subsequently differentiate into the morphologically and functionally distinct segments of the mature nephron. Here, we have used an allelic series of mutations to determine the role of the secreted signaling molecule FGF8 in nephrogenesis. In the absence of FGF8 signaling, nephron formation is initiated, but the nascent nephrons do not express Wnt4or Lim1, and nephrogenesis does not progress to the S-shaped body stage. Furthermore, the nephron progenitor cells that reside in the peripheral zone, the outermost region of the developing kidney, are progressively lost. When FGF8 signaling is severely reduced rather than eliminated, mesenchymal cells differentiate into S-shaped bodies. However, the cells within these structures that normally differentiate into the tubular segments of the mature nephron undergo apoptosis, resulting in the formation of kidneys with severely truncated nephrons consisting of renal corpuscles connected to collecting ducts by an abnormally short tubular segment. Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis. |
| Databáze: | OpenAIRE |
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