Control of tissue morphology by Fasciclin III-mediated intercellular adhesion.
Morphogenesis is dependent on the orchestration of multiple developmental processes to generate mature functional organs. However, the signalling pathways that coordinate morphogenesis and the mechanisms that translate these signals into tissue shape changes are not well understood. Here, we demonstrate that changes in intercellular adhesion mediated by the transmembrane protein Fasciclin III (FasIII) represent a key mediator of morphogenesis. Using the embryonic Drosophila hindgut as an in vivo model for organogenesis, we show that the tightening of hindgut curvature that normally occurs between embryonic stage 12 and 15 to generate the characteristic shepherd's crook shape is dependent on localised JAK/STAT pathway activation. This localised pathway activity drives the expression of FasIII leading to its subcellular lateralisation at a stage before formation of septate junctions. Additionally, we show that JAK/STAT- and FasIII-dependent morphogenesis also regulates folds within the third instar wing imaginal disc. We show that FasIII forms homophilic intercellular interactions that promote intercellular adhesion in vivo and in cultured cells. To explore these findings, we have developed a mathematical model of the developing hindgut, based on the differential interfacial tension hypothesis (DITH) linking intercellular adhesion and localised surface tension. Our model suggests that increased intercellular adhesion provided by FasIII can be sufficient to drive the tightening of tube curvature observed. Taken together, these results identify a conserved molecular mechanism that directly links JAK/STAT pathway signalling to intercellular adhesion and that sculpts both tubular and planar epithelial shape.
MRC Centre for Developmental and Biomedical Genetics, The University of Sheffield, Firth Court, Sheffield S10 2TN, UK.
Richard E
RE
Wells
Joseph D
JD
Barry
Samantha J
SJ
Warrington
Simon
S
Cuhlmann
Paul
P
Evans
Wolfgang
W
Huber
David
D
Strutt
Martin P
MP
Zeidler
D000818:Animals; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000166:cytology* / Q000196:embryology / Q000201:enzymology; D041981:Gastrointestinal Tract / Q000033:anatomy & histology* / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C061565:Fas3 protein, Drosophila; D050791:STAT Transcription Factors; D053612:Janus Kinases
Adhesion; Drosophila; Modelling; Mouse; Organogenesis