Interstitial Flow,Zebrafish,and Lymphatic Vascular Development

In the current issue of Lymphatic Research and Biology, Wilson et al. have successfully explored the confluence of two important, recent approaches to expand our understanding of normal and disturbed lymphatic function, namely, exploration of the physiological impact of interstitial flow upon lymphatic function, and the use of the zebrafish (Danio rerio) to explore intricate developmental biology of vascular, and more specifically, lymphatic vascular development. ¹

The critical role of interstitial flow upon postnatal lymphatic regeneration was first underscored by Boardman and Swartz ² through their novel use of collagen implants interposed within the surgically altered murine tail, thereby demonstrating that interstitial channel formation antedates lymphatic endothelial cell responses, which are initiated primarily in the direction of interstitial fluid flow. Subsequent investigative approaches to this question continue to suggest that lymphatic growth is dependent upon pre-existing interstitial flow.^3–5

In the current study, Wilson et al. have postulated that, in a similar fashion, interstitial fluid flow may function as an important morphoregulator during developmental lymphangiogenesis. In order to address this important question regarding early developmental events, the authors have turned to the zebrafish for answers. In recent years, because of its many favorable attributes (including optical clarity and rapid stages of vascular development) this model system has proven to be very favorable to studies of lymphatic vascular development. ⁶

Here, the authors have pharmacologically modulated interstitial flow in a mutant fish line. Augmentation or diminution of interstitial flow has a remarkable effect upon lymphatic patterning and can elicit a lymphedema-like patterning.

These observations are novel and important, providing yet another avenue for continued investigation into the forces that govern health and disease in both developing and mature lymphatic vasculature.