Modeling flow in embryonic lymphatic vasculature: what is its role in valve development?

Abstract

A majority of lymphatic valves tend to form in proximity to vessel junctions, and it is often proposed that disturbed flow at junctions creates oscillating shear stress that leads to accumulation of transcription factors which bring about valvogenesis at these sites. In images of networks of dorsal skin lymphatics from embryonic mice (day E16), we compared simulated fluid flow patterns and observed distributions of the transcription factor Prox1, which is implicated in valve formation. Because of creeping-flow conditions, flow across vessel junctions was not 'disturbed', and within a given vessel, shear stress varied inversely with local conduit width. Prox1 concentration was indeed localised to vessel end-regions, but over three networks was not consistently correlated with the vessel normalised-distance distribution of either fluid shear stress or shear-stress axial gradient. These findings do not support the presently accepted mechanism for the role of flow in valve localisation.

Keywords

• valvogenesis
• valve localization
• lymphatic development
• lymphatic vessel network
• fluid shear stress
• shear stress gradient