Lymphatic development in mouse small intestine

Abstract

Lymphatic vessels in the small intestine serve as essential conduits for the absorption and transport of lipids from the intestine to the thoracic duct. Although the morphology and function of the intestinal lymphatic vasculature are well known, little is known about the embryonic development of these vessels. In this study, we examined development of lymphatic and blood vasculatures in the intestinal tube during mouse embryonic development by immunostaining with recently discovered molecular markers for lymphatic endothelial cells: LYVE-1, VEGFR3, Prox-1, and podoplanin. Immature lymphatics became detectable in mesentery, but not in intestinal tube, around E13.5-E14.5, while organized lymphatic vessel plexuses and capillaries were observed in intestinal tube and villi around E17.5. These lymphatic plexuses and capillaries in the intestinal tube appeared to be formed through an active branching process associated with activation of VEGFR3 and involvement of LYVE-1؉ macrophages. Our data also reveal that the lymphatic vessels in the intestinal tube, unlike the blood vessels, have not originated from the mesoderm of intestine. All lymphatic vessels in the intestinal tube originated by extension of mesenteric lymphatic vessels through an active branching process. Although the formation of lymphatic vessels follows the formation of blood vessels in the intestine, a mature lymphatic vasculature is formed before birth. Together, our study reveals the temporal and spatial windows of intestinal lymphatic development during embryonic development in mouse. Developmental Dynamics 236:2020 -2025, 2007.

Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver

“…This result might give insight into the lymphangiogenesis during normal liver development. [14][15][16] We also detected podoplanin in nerve fascicles, mesothelium covering the liver surface, and stromal cells around the intrahepatic large bile ducts but not in biliary epithelial cells. Schacht et al, 2 detected podoplanin in biliary epithelial cells of normal liver using tissue microarrays.…”

Lymph flow regulates collecting lymphatic vessel maturation in vivo

“…Similarly, examination of the thoracic duct at E18.5 revealed only scattered SMCs in the WT embryo but abundant SMC coverage of the dilated CLEC2- the mesenteric lymphatic network remodels to form a hierarchical set of collecting vessels in which smaller vessels near the gut wall feed into larger vessels that are more distant from the gut wall (ref. 23 and Figure 3). Since the remodeling process that creates the final lymphatic collecting vessel network takes place at the same time that valves form, we hypothesized that it might also be driven by fluid shear force and therefore disrupted in CLEC2-deficient animals.…”

“…Although primary lymphatic vessels form normally, Clec2 -/-animals exhibit severe cutaneous edema by E14 and both chylous ascites and chylothorax after birth (20,22), phenotypes suggestive of lymphatic dysfunction due to obstruction. To determine if the presence of blood in lymphatic vessels obstructs lymph flow during lymphatic development in Clec2 -/-animals, we first examined the intestine histologically between E15.5 and E18.5, the time period during which lymphatic vessels invade the gut and presumably begin to carry lymph from that organ (23). Edema was not observed in either control or CLEC2-deficient intestines at E15.5, but Clec2 -/-animals exhibited significant intestinal-wall edema at E16.5 and marked edema at E18.5 compared with control littermates (Figure 1, A-F, and I).…”

“…LECs grow into the mesentery along preexisting blood vessels and reach the developing intestine by E15, a timepoint prior to the onset of lymphatic flow (11,23). This nonfunctional, primary mesenteric lymphatic network is composed of highly branched vessels of similar diameter.…”

Tbx1 regulatesVegfr3and is required for lymphatic vessel development

“…In the mouse, the first mesenteric lymphatic vessels form around E13 (van der Putte, 1975;Kim et al, 2007). To monitor Tbx1 expression, we were seen (Fig.…”