Zebrafish lacking Tcf2 develop multiple lumens (arows) in the gut.


All biological tubes consist of a single lumen. According to Michel Bagnat, Didier Stainier, and colleagues (University of California, San Francisco, CA), one way to ensure this singularity is to use fluid pressure.

Too many lumens are found in the gut of Zebrafish larvae lacking the Tcf2 transcription factor. Extra tubes remain because they fail to coalesce normally during development. Bagnat and colleagues guessed that coalescence might be controlled by genes under Tcf2's control.

DNA microarrays revealed that the gene for an epithelial junction protein, called claudin 15, was down-regulated in tcf2 mutants. Claudins form pores between cells that allow ions to be transported across epithelia down an electrochemical gradient. Tcf2 mutant gut cells also lacked a Na+/K+ ATPase, which probably creates the gradient that drives ions through the pores.

Where ions flow, water is sure to follow, resulting in lumenal fluid build-up. In vitro, Claudin 15 plus ion flow encouraged small neighboring lumens to unite. The authors hypothesize that pressure from the fluid forces lumens to join together, but cell rearrangements must also occur.

Fluid accumulation probably promotes single lumen formation in structures such as the pancreas, which begins with multiple small lumens, and the neural tube, where fluid accumulation is tightly regulated.


Bagnat, M., et al.
Nat. Cell Biol.