During early embryonic development (E12-14) renin expressing cells are present in the undifferentiated metanephric mesenchyme before kidney vascularization has occurred and before the hemodynamic functions of renin are needed. Later in fetal life (E17-20) renin expressing cells are found in large intrarenal arteries. As maturating continues, renin-expressing cells become progressively restricted to the classical juxtaglomerular localization found in the adult mammal. If an adult mammal is subjected to manipulations known to increase renin synthesis, there is a recruitment of renin expressing cells along the preglomerular arteries and in the kidney interstitium resembling the embryonic pattern. These data suggest that renal vascular and interstitium cells have the plasticity to develop phenotypic characterizations of renin expressing cells. It is likely that the ability of adult kidney cells to re-express the renin gene and acquire the JG cell phenotype depends on the developmental history of the cell in question. However, the embryologic origin and the functions of JG cells during kidney embryogenesis are unknown. We hypothesis that (1) the JG cells originate from the kidney cells rather than from invading extrarenal vessels, (2) The lineage of JG cells is that of smooth muscle or interstitial cells, (3) Expression of renin is responsible of JG cell differentiation, (4) JG cells are involved in nephrogenesis and microvascular development of the kidney. The following specific aims will be pursued: (i) Define the phenotypic characteristics of JG cells during maturation, (ii) Determine the site of origin of JG cells; (iii) Identify and follow the fate of JG cell precursors in vitro and in vivo; (iv) Define whether the JG cell is necessary for normal nephrogenesis and vascular development. The studies should generate fundamental knowledge on JG cell differentiation and function during kidney embryogenesis. By providing new models, the studies should also open new avenues for understanding, treatment and prevention of hypertension and kidney diseases.
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