A molecular and genetic analysis of renalglomerular capillary development.

The adult kidney is highly vascular and receives about 20% of the cardiac output, yet the mode of development of the glomerular capillaries is not fully understood. At the inception of nephrogenesis the condensed metanephric mesenchyme contains no patent capillaries. However, in this current study we detected vascular endothelial growth factor (VEGF) mRNA and protein in uninduced mouse E11 metanephric mesenchyme and in cell lines from this tissue. Moreover, transcripts for receptor tyrosine kinases which are markers of endothelial precursors (VEGFR-1/Flt-1, VEGFR-2/Flk-1 and Tie-1) were expressed by the E11 mesenchyme. In transgenic mice, Tie1/LacZ-expressing cells were identified in E11 renal mesenchyme when patent vessels were absent. Moreover, a similar pattern of transgene expression was detected within intermediate mesoderm condensing to form metanephric mesenchyme. When Tie-1/LacZ E11 metanephroi were transplanted into the nephrogenic cortex of wild-type mice, transgene-expressing capillary loops were detected in glomeruli developing in donor tissue. In contrast, glomerular Tie-1/LacZ-positive vessels never developed in rudiments in organ culture. We postulate that endothelial precursors are present at the inception of the mouse nephrogenesis, and these differentiate and undergo morphogenesis into glomerular capillaries when experimental conditions resemble those found in the metanephros in vivo.