Epithelial Polarity & Cell Division
Epithelial tissues act as essential mechanical barriers to the external environment, and must also display plasticity to accommodate morphogenesis, growth and homeostatic proliferation. We investigate how epithelial apico-basal organization copes with the challenge of cell division and propagates itself to the emerging daughter cells, maintaining tissue architecture and function.
A critical property of epithelial cells is their ability to establish functional and molecular asymmetries along an apico-basal axis, termed apico-basal polarity. This is so inseparable from epithelial function that its disruption invariably has critical consequences for development and is also linked to many human pathologies, including cancer. Apico-basal polarization is achieved by evolutionarily conserved polarity proteins that are distributed asymmetrically and position intercellular junctions to regulate paracellular diffusion and adhesion.
We aim to understand how the polarized cues of an epithelium promote faithful cell separation and propagate epithelial organization during cell division by addressing three mains questions:
1) How is the cell cycle coupled with the reorganization of apico-basal polarity determinants?
2) How to make cytokinesis a polarized and efficient process in a multicellular context?
3) How to transmit epithelial polarity to the emerging daughter cells?
Using Drosophila, we combine the power to image intact multicellular tissues with an expanding genetic toolkit, including genome-wide RNAi libraries and genomic engineering with CRISPR/CAS9. Moreover, we are implementing optogenetic tools to interfere with protein function with high spatiotemporal control. Our findings revealed that the polarity machinery is tightly orchestrated with the cell cycle to position the new daughter cells within the epithelial monolayer (Carvalho et al., 2015), which is essential for proper development and homeostasis. Based on the conservation of the molecular mechanisms that control epithelial organization from Drosophila to Humans, our works aims at providing fundamental mechanistic insight to tackle disease.
Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC. Development147(15):, 2020. [Journal: Article] [IF: 5,6 (*)]
DOI: 10.1242/dev.186593 SCOPUS: 85089300645. .
Moreira S., Osswald M., Ventura G., Gonçalves M., Sunkel C.E., Morais-de-Sá E.,
PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity. Cell Reports26(2):293-301.e7, 2019. [Journal: Article] [CI: 7] [IF: 8,1]
DOI: 10.1016/j.celrep.2018.12.060 SCOPUS: 85059397223. .
Osswald M., Morais-de-Sá E.,
Dealing with apicalbasal polarity and intercellular junctions: a multidimensional challenge for epithelial cell division. Current Opinion in Cell Biology60:75-83, 2019. [Journal: Review] [CI: 1] [IF: 8,2]
DOI: 10.1016/j.ceb.2019.04.006 SCOPUS: 85066055206. .
Carvalho C.A., Moreira S., Ventura G., Sunkel C.E., Morais-De-Sá E.,
Aurora a triggers Lgl cortical release during symmetric division to control planar spindle orientation. Current Biology25(1):53-60, 2015. [Journal: Article] [CI: 53] [IF: 9]
DOI: 10.1016/j.cub.2014.10.053 SCOPUS: 84920415073. .
Morais-De-Sá E., Sunkel C.,
Adherens junctions determine the apical position of the midbody during follicular epithelial cell division. EMBO Reports14(8):696-703, 2013. [Journal: Article] [CI: 55] [IF: 7,9]
DOI: 10.1038/embor.2013.85 SCOPUS: 84881480225. .
Morais-de-Sá E., Mirouse V., St Johnston D.,
aPKC Phosphorylation of Bazooka Defines the Apical/Lateral Border in Drosophila Epithelial Cells. Cell141(3):509-523, 2010. [Journal: Article] [CI: 184] [IF: 32,4]
DOI: 10.1016/j.cell.2010.02.040 SCOPUS: 77951911203. .
Osswald M., Santos A.F., Morais-De-sá E.,
Light-induced protein clustering for optogenetic interference and protein interaction analysis in drosophila S2 cells. Biomolecules9(2):, 2019. [Journal: Article] [CI: 3] [IF: 4,1]
DOI: 10.3390/biom9020061 SCOPUS: 85061569009. .
Afonso O., Castellani C.M., Cheeseman L.P., Ferreira J.G., Orr B., Ferreira L.T., Chambers J.J., Morais-De-Sá E., Maresca T.J., Maiato H.,
Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk. eLife8:, 2019. [Journal: Article] [CI: 9] [IF: 7,1]
DOI: 10.7554/eLife.47646 SCOPUS: 85071529547. .
Melo S., Figueiredo J., Fernandes M.S., Gonçalves M., Morais-De-Sá E., Sanches J.M., Seruca R.,
Predicting the functional impact of CDH1 missense mutations in hereditary diffuse gastric cancer. International Journal of Molecular Sciences18(12):, 2017. [Journal: Review] [CI: 21] [IF: 3,7]
DOI: 10.3390/ijms18122687 SCOPUS: 85038807279. .