α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium.

The spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and β-Spectrin are essential to maintain a monolayered FE, but, contrary to previous work, spectrins are not required to control proliferation. Furthermore, spectrin mutant cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-Spectrin and integrin mutant cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-Myosin II pathway enhances and decreases multilayering of α-Spectrin cells, respectively. Similarly, higher Myosin II activity enhances the integrin multilayering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequate forces, in order to maintain a monolayered epithelium.BFN was supported by Singapore Ministry of Education; GKS by the BBSRC; IAG by the Wellcome Trust, the BBSRC and the Isaac Newton Trust (Cambridge, UK); CSCM and MDMB by the “Ministerio de Economía y Competiti vidad”,the FEDER programme (BFU2013-48988-C2-1-P), and Junta de Andalucía (Proyecto de Excelencia P09-CVI-5058); IG by a JAE-DOC (CSIC); and IMP by the Wellcome Trust, the BBSRC, the Department of Zoology (Cambridge) and the University of Cambridge.This is the final version of the article. It first appeared from the Company of Biologists via https://doi.org/10.1242/dev.13007

α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium

The Spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of Spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and β-Spectrin are essential to maintain a mono-layered FE, but, contrary to previous work, Spectrins are not required to control proliferation. Furthermore, spectrin cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-spectrin and integrin cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-myosin-II pathway enhances and decreases multi-layering of α-spectrin cells, respectively. Similarly, higher myosin-II activity enhances the integrin multi-layering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. All together, we suggest that a functional Spectrin-Integrin complex is essential to balance adequate forces, in order to maintain a mono-layered epithelium.This work was supported by the Singapore Ministry of Education [Master Scholarship EDUN N23-03-044 to B.F.N.]; the Biotechnology and Biological Sciences Research Council (BBSRC) [RG42522 to I.A.G.; BB/L001748/1 to G.K.S. and I.M.P.]; the Wellcome Trust [087899/Z/08/Z to I.A.G. and I.M.P.]; the Isaac Newton Trust (Cambridge, UK) [11.35(af ) to I.A.-G.]; the FEDER programme [BFU2013-48988-C2-1-P to C.S.-C.M. and M.D.M.-B.]; Junta de Andalucía [Proyecto de Excelencia P09-CVI-5058 to C.S.-C.M. and M.D.M.-B.]; a Superior Council for Scientific Research (CSIC) JAE-DOC (to I.G.); and the Department of Zoology (Cambridge) and the University of Cambridge (I.M.P.).Peer Reviewe