Dual origin of avian lymphatics

Abstract

The earliest signs of the lymphatic vascular system are the lymph sacs, which develop adjacent to specific embryonic veins. It has been suggested that sprouts from the lymph sacs form the complete lymphatic vascular system. We have studied the origin of the jugular lymph sacs (JLS), the dermal lymphatics and the lymph hearts of avian embryos. In day 6.5 embryos, the JLS is an endothelial-lined sinusoidal structure. The lymphatic endothelial cells (LECs) stain (in the quail) positive for QH1 antibody and soybean agglutinin. As early as day 4, the anlagen of the JLS can be recognized by their Prox1 expression. Prox1 is found in the jugular section of the cardinal veins, and in scattered cells located in the dermatomes along the cranio-caudal axis and in the splanchnopleura. In the quail, such cells are positive for Prox1 and QH1. In the jugular region, the veins co-express the angiopoietin receptor Tie2. Quail-chick-chimera studies show that the peripheral parts of the JLS form by integration of cells from the paraxial mesoderm. Intra-venous application of DiI-conjugated acetylated low-density lipoprotein into day 4 embryos suggests a venous origin of the deep parts of the JLS. Superficial lymphatics are directly derived from the dermatomes, as shown by dermatome grafting. The lymph hearts in the lumbo-sacral region develop from a plexus of Prox1-positive lymphatic capillaries. Both LECs and muscle cells of the lymph hearts are of somitic origin. In sum, avian lymphatics are of dual origin. The deep parts of the lymph sacs are derived from adjacent veins, the superficial parts of the JLS and the dermal lymphatics from local lymphangioblasts.

Mesenchymal cells with leukocyte and lymphendothelial characteristics in murine embryos

“…According to them, the lymphatics develop by confluence of mesenchymal cells, and only the lymph sacs might be of venous origin (Kampmeier, 1912a). Our recent studies on avian embryos have supported the latter view (Wilting et al, 2006). Intravenous application of DiI-conjugated acetylated low-density-lipoprotein, which labels endothelial cells, into day-4 embryos, has revealed labelling of the JLS at day 6.5.…”

“…The main parts of the lymph sacs are obviously derived from adjacent venous segments. Peripheral parts of the lymph sacs and the dermal lymphatics seem to be mainly derived from local lymphangioblasts (Wilting et al, 2006). Lymphangioblasts have very recently also been observed in Xenopus tadpoles (Ny et al, 2006).…”

Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature

“…The interaction of Tie2 with its ligand angiopoietin-1 (Ang1) helps remodel and stabilize primitive vasculature (Sato et al 1993;Suri et al 1996). The phenotype of mice lacking another Tie2 ligand, Ang2, suggested that Tie2 also functions during postnatal lymphatic remodeling (Gale et al 2002); however, its expression has not been observed in LECs (Motoike et al 2000;Saban et al 2004;Wilting et al 2006), except in restricted regions of adult lymphatics Tammela et al 2005). Hence, Tie2-independent, integrin-mediated signaling might mediate angiopoietin function in the lymphatic vasculature .…”

Vascular Development in the Zebrafish

“…These molecular tools have, for example, permitted reexamination of the question of the embryonic origins of the first lymphatic endothelial cells (LECs), in particular whether they are derived from primitive venous endothelium or arise de novo from mesenchyme. Grafting studies in avian embryos (Wilting et al 2000;Wilting et al 2006) and analysis of a lymphatic marker, Prox1 (Wigle and Oliver 1999), in Xenopus tadpoles (Ny et al 2005) suggest that lymphatics arise from both embryonic veins and mesenchyme. Genetic studies in mice, however, indicate a venous origin for the first LECs, showing the expression of Prox1 in a subset of venous endothelial cells and migration of Prox1 positive cells from veins to form lymph sacs (Karkkainen et al 2004).…”