Alvers, A.L., Ryan, S., Scherz, P.J., Huisken, J., and Bagnat, M. (2014) Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling. Development (Cambridge, England). 141(5):1110-1119.
The formation of a single lumen during tubulogenesis is crucial for the development and function of many organs. Although
3D cell culture models have identified molecular mechanisms controlling lumen formation in vitro, their function during vertebrate organogenesis is poorly understood. Using light sheet microscopy and genetic approaches
we have investigated single lumen formation in the zebrafish gut. Here we show that during gut development multiple lumens
open and enlarge to generate a distinct intermediate, which consists of two adjacent unfused lumens separated by basolateral
contacts. We observed that these lumens arise independently from each other along the length of the gut and do not share a
continuous apical surface. Resolution of this intermediate into a single, continuous lumen requires the remodeling of contacts
between adjacent lumens and subsequent lumen fusion. We show that lumen resolution, but not lumen opening, is impaired in
smoothened (smo) mutants, indicating that fluid-driven lumen enlargement and resolution are two distinct processes. Furthermore, we show
that smo mutants exhibit perturbations in the Rab11 trafficking pathway and demonstrate that Rab11-mediated trafficking is necessary
for single lumen formation. Thus, lumen resolution is a distinct genetically controlled process crucial for single, continuous
lumen formation in the zebrafish gut.