Genetic control of single lumen formation in the zebrafish gut.
Most organs consist of networks of interconnected tubes that serve as conduits to transport fluid and cells and act as physiological barriers between compartments. Biological tubes are assembled through very diverse developmental processes that generate structures of different shapes and sizes. Nevertheless, all biological tubes invariably possess one single lumen. The mechanisms responsible for single lumen specification are not known. Here we show that zebrafish mutants for the MODY5 and familial GCKD gene tcf2 (also known as vhnf1) fail to specify a single lumen in their gut tube and instead develop multiple lumens. We show that Tcf2 controls single lumen formation by regulating claudin15 and Na+/K+-ATPase expression. Our in vivo and in vitro results indicate that Claudin15 functions in paracellular ion transport to specify single lumen formation. This work shows that single lumen formation is genetically controlled and appears to be driven by the accumulation of fluid.
Bagnat
Michel
M
Department of Biochemistry & Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, 1550 Fourth Street, San Francisco, California 94158-2324, USA. michel.bagnat@ucsf.edu
Cheung
Isla D
ID
Mostov
Keith E
KE
Stainier
Didier Y R
DY
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D057167:Claudins; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007422:Intestines / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D007473:Ion Channels / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D057167:Claudins; D007473:Ion Channels; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C459596:claudin 15; C496498:hnf1ba protein, zebrafish; D051539:Hepatocyte Nuclear Factor 1-beta; D000254:Sodium-Potassium-Exchanging ATPase