Important parallels with mechanisms of tumor vascularization.

Four-dimensional analysis of vascularization during primary development of an organ, the gonad.

Douglas Coveney ...... Department of Cell Biology, Duke University Medical Center, Durham, NC 27710


Time-lapse microscopy has advanced our understanding of yolk sac and early embryonic vascularization. However, it has been difficult to assess endothelial interactions during epithelial morphogenesis of internal organs.
To address this issue we have developed the first time-lapse system to study vascularization of a mammalian organ in four dimensions.

We show that vascularization of XX and XY gonads is a highly dynamic, sexually dimorphic process.

The XX gonad recruits vasculature by a typical angiogenic process.

In contrast, the XY gonad recruits and patterns vasculature by a novel remodeling mechanism beginning with breakdown of an existing mesonephric vessel.

Subsequently, in XY organs individual endothelial cells migrate and reaggregate in the coelomic domain to form the major testicular artery.
Migrating endothelial cells respect domain boundaries well before they are morphologically evident, subdividing the gonad into 10 avascular regions where testis cords form.

This model of vascular development in an internal organ has a direct impact on the current dogma of vascular integration during organ development and presents important parallels with mechanisms of tumor vascularization.

Published online on May 14, 2008, Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707674105