The vertebrate lymphatic vascular network provides crucial circulatory and immune functions but its developmental origin has been a contentious issue, in particular the question of whether lymphatic endothelial cells (LECs) have an exclusively venous origin. Now, Natasha Harvey, Mathias Francois and colleagues investigate the origin of LECs in the mouse embryonic dermis. Cell fate markers reveal that, in addition to LECs arising from the flanks and migrating towards the midline, discrete ‘clusters’ of LECs originate more medially. These LEC clusters arise between 13.5 and 16.5 dpc, and proliferate before being incorporated into the main lymphatic network. Lineage tracing reveals that LEC clusters have an endothelial origin but do not arise from haemogenic endothelium; rather, they derive from the skin's capillary endothelial network, which at the time is not committed to either a venous or arterial fate. Further lineage and genetic analysis reveals that, once specified by Prox1, LECs require Ccbe1 to leave the capillary network, and the authors demonstrate that excess VEFGC signalling increases the number of medial LEC progenitors. The work reveals an additional local source for LECs that may facilitate the network's rapid development, and raises the question of whether other local sources help build lymphatic networks elsewhere in the embryo.
Building lymphatic networks: thinking local in the dermis
Building lymphatic networks: thinking local in the dermis. Development 15 May 2018; 145 (10): e1003. doi:
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