The mammalian kidney and reproductive systems both derive from a common embryological origin, the intermediate mesoderm. Abnormal intermediate mesoderm development can result in congenital abnormalities of the urogenital system, yet the molecular mechanisms that govern intermediate mesoderm development are incompletely defined. The spatial and temporal expression of the proteins BMP2 and 4 and their receptor ALK3, in urogenital tissue, suggests a function for BMP-ALK3 signaling in the intermediate mesoderm. It was found that Alk3IM null kidneys display renal hypoplasia, associated with a decrease in kidney size and nephron number. The phenotype of renal hypoplasia in Alk3IM nulls was associated with early decreased number of developing nephron structures and secondary defects in branching morphogenesis. While neither apoptosis nor cell proliferation differed in metanephric mesenchyme cells in Alk3IM nulls, markers of renal progenitor cells were decreased in mutant animals. It was observed that Alk3 expression in the intermediate mesoderm also controls mesonephric tubule number. Alk3IM nulls had fewer mesonephric tubules and fewer derivative Leydig cells. The reduction in Leydig cells resulted in decreased levels in serum testosterone and defects in seminal vesicle formation and fertility. Alk3 expression was also required for normal development of the corpus epididymis. The morphological defects in nephrogenesis were associated with decreased phospho-p38 MAPK expression and in the testis with decreased Phospho-SMAD1/5/8. These results elucidated a requirement for Alk3 signaling in controlling progenitor cells derived from the intermediate mesoderm.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/26166 |
| Date | 15 February 2011 |
| Creators | Di Giovanni, Valeria |
| Contributors | Rosenblum, Norman D. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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