Lumen formation is a critical event in biological tube formation, yet its molecular mechanisms remain poorly understood. Specifically, how lumen expansion is coordinated with other processes of tubulogenesis is not well known, and the role of membrane transporters in tubulogenesis during development has not been adequately addressed. Here we identify a solute carrier 26 (Slc26) family protein as an essential regulator of tubulogenesis using the notochord of the invertebrate chordate Ciona intestinalis as a model. Ci -Slc26aα is indispensable for lumen formation and expansion, but not for apical/luminal membrane formation and lumen connection. Ci -Slc26aα acts as an anion transporter, mediating the electrogenic exchange of sulfate or oxalate for chloride or bicarbonate and electroneutral chloride:bicarbonate exchange. Mutant rescue assays show that this transport activity is essential for Ci -Slc26aα’s in vivo function. Our work reveals the consequences and relationships of several key processes in lumen formation, and establishes an in vivo assay for studying the molecular basis of the transport properties of SLC26 family transporters and their related diseases.
Apico-basal polarization is a crucial step in the de novo formation of biological tubes. In Ciona notochord, tubulogenesis occurs in a single file of cells in the absence of cell proliferation. This configuration presents a unique challenge for the formation of a continuous lumen. Here, we show that this geometric configuration is associated with a novel polarization strategy: the generation of bipolar epithelial cells possessing two apical/luminal domains instead of one, as in the conventional epithelium. At the molecular level, cells establish two discrete Par3/Par6/aPKC patches, and form two sets of tight junctions, in opposite points of the cells. The key molecule controlling the formation of both domains is Par3. Changing the position of the cells within the organ fundamentally changes their polarity and the number of apical domains they develop. These results reveal a new mechanism for tubulogenesis from the simplest cell arrangement, which occurs in other developmental contexts, including vertebrate vascular anastomosis.
High mortalities of the bluefin tuna Thunnus thynnus reared in Adriatic Sea cages occurred during spring 2004. Outbreaks had been previously reported at the same facility in similar conditions in the tuna population harvested in winter 2003. Fish displayed no external clinical signs of disease except for changed coloration and atypical swimming, and gross pathology was limited to general signs of septicemia. Histological and bacteriological findings suggested an epizootic outbreak of pasteurellosis. The pathology suggested an acute infection with the changes characteristic of septicemia. Most fish died in 1–2 d without gross pathology, possibly because of the virulence of the bacterial strain or reduced resistance of the fish. A low percentage of fish developed a chronic form of infection with disseminated granulomas in kidneys but also showed no gross pathology. Tuna parasitofauna was evaluated and did not appear to affect the development and the course of the disease.