Direct visualization of renal vascular morphogenesis in flk1
heterozygous mutant mice.
Robert, Barry, Patricia L. St. John, and Dale R. Abrahamson.
Departments of Comparative Medicine and Cell Biology, University of
Alabama at Birmingham, Birmingham, Alabama 35294-0019
APStracts 5:0066F, 1998.
Flk1, a receptor tyrosine kinase for vascular endothelial growth
factor (VEGF), is the earliest known marker for endothelial
precursors (angioblasts). We examined heterozygote mice in which the
Flk1 gene was partially replaced by a promoterless LacZ insert, and
used -galactosidase histochemistry to view cells transcribing Flk1.
In E10 embryos, a Flk1 positive network surrounded the metanephric
blastema, and at E11, a vessel entered the metanephros from its
ventral aspect alongside the ingrowing ureteric bud. Aortic branches
did not engage embryonic kidneys at these time points, however. In
newborns, - galactosidase was localized exclusively and intensely to
endothelial cells of all vessels and glomeruli. In contrast, when E12
kidneys grown in organ culture for 6d were examined, only scattered
Flk1 positive cells were seen; glomeruli were unlabeled and vessels
were absent. When organ cultured kidneys were then grafted into wild
-type anterior eye chambers, numerous Flk1 positive endothelial cells
in vessels and glomeruli were found, all stemming from the graft.
Image analysis showed that grafts with the most abundant glomerulo-
and tubulogenesis were also those with the richest expression of
Flk1. We conclude: (a) kidney microvessels precede renal artery
development; (b) angioblast differentiation is arrested in organ
culture but released upon grafting when vasculogenesis resumes, and
(c) nephrogenesis and microvessel assembly are tightly coupled in
vivo.
Received 12 December 1997; accepted in final form 5 March 1998.
APS Manuscript Number F394-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 6 April 1998