Cytoskeleton in Development and Disease

Our lab investigates how cells remodel their microtubule cytoskeleton to support diverse cellular functions. Microtubule polymers are fundamental structural components of eukaryotic cells, playing essential roles in establishing and maintaining cell shape, polarity, migration, and division. These polymers are generated by microtubule-organizing centers (MTOCs), with the centrosome being the main MTOC in dividing cells.

However, most cells in living organisms are not actively dividing; instead, they exit mitosis and/or differentiate into specialized cell types, such as neurons and epithelial cells. In these cells, centrosomes stop generating microtubules, which are instead organized from other cellular locations through acentrosomal pathways. In contrast to centrosomes, whose composition and regulation are well understood, comparatively little is known about the spatial and temporal control of microtubule generation through acentrosomal mechanisms.

We use Drosophila and human oocytes as model systems and combine cellular and developmental biology with advanced imaging, genetics, and biochemical approaches to investigate how specific sites within cells acquire microtubule-organizing activity and how these mechanisms contribute to essential physiological processes.

Answering these questions is key to understanding how microtubule organization supports normal development and how its deregulation contributes to diseases linked to cytoskeletal dysfunction, including infertility and cancer.

Projects

31-03-27 | MT_Makeover
Funded by: Fundação para a Ciência e Tecnologia
This project investigates how cells of the female germ-line remodel their microtubule cytoskeleton during oogenesis. We are currently dissecting the mechanisms driving acentrosomal microtubule assembly to reveal how specialized microtubule networks are formed and how their deregulation contributes to infertility.

Publications

Lince-Faria M, Ferreira-Silva A, Pimenta-Marques A. The Centriole Stability Assay: A Method to Investigate Mechanisms Involved in the Maintenance of the Centrosome Structure in Drosophila Cultured Cells. BIO-PROTOCOL (2025) 15 1373 (https://doi.org/10.21769/bioprotoc.5330).
Pimenta-Marques A, Perestrelo T, Reis-Rodrigues P, Duarte P, Ferreira-Silva A, Lince-Faria M, Bettencourt-Dias M. Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase and the PCM. EMBO Reports (2024) 25: 102-127. (https://doi.org/10.1038/s44319-023-00020-6)
Pimenta-Marques A, Bettencourt-Dias M. Pericentriolar Material. Current Biology (2020) 30 12, R687-689. (https://doi.org/10.1016/j.cub.2020.04.064)
Werner S, Pimenta-Marques A, Bettencourt-Dias M. Maintaining centrosomes and cilia. Journal of Cell Science (2017) 130 22: 3789-3800. (https://doi.org/10.1242/jcs.203505)
Pimenta-Marques A, Bento I, Lopes C.A.M, Duarte P, Jana S.C, Bettencourt-Dias M. A mechanism for the elimination of the female gamete centrosome in Drosophila melanogaster". Science (2016) 353 6294. (DOI: 10.1126/science.aaf4866)
Cunha-Ferreira I, Bento I, Pimenta-Marques A, Jana, S.C, Lince-Faria M, Duarte P, Borrego-Pinto J, et al. Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number. Current Biology (2013) 23 22 2245-2254. (https://doi.org/10.1016/j.cub.2013.09.037)
Guilgur L.G., Prudêncio P, Ferreira T, Pimenta-Marques A, Martinho R.G. Drosophila aPKC is required for mitotic spindle orientation during symmetric division of epithelial cells. Development 139 3 (2012) 503-513. (https://doi.org/10.1242/dev.071027).
van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho R.G, Gevaert K, Arnesen T. NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation. PLoS Genetics (2011) 7 7. (https://doi.org/10.1371/journal.pgen.1002169).
Pimenta-Marques A, Tostões R, Marty T, Barbosa V, Lehmann R, Martinho R.G. Differential requirements of a mitotic acetyltransferase in somatic and germ line cells. Developmental Biology (2008) 323 2 197-206. (https://doi.org/10.1016/j.ydbio.2008.08.021).

Prizes and Awards

Awards to PI (Ana Pimenta-Marques):

2025 – FCT Exploratory Grant | Uncovering Novel Regulatory Pathways of Microtubule Organization During Cellular Differentiation.
2021 - 3rd place for best oral presentation. Portuguese Drosophila Meeting, Portugal, Molecular Regulation of Centrosome Stability.
2021 - Exploratory Grant | FCT | Microtubule organization in Human oocytes.
2020 - Investigator Contract: FCT Stimulus of Scientific Employment (CEEC-IND; FCT).
2017 – FCT Grant | Regulation of microtubule organizing centers during development.
2016 - Medals of Honor L’Oréal for Women in Science 2016 (L’Oreal Foundation, FCT and UNESCO).
2018 – FCT Post-Doctoral Contract
2011 – FCT Post-Doctoral Fellowship
2009 – Travel grant from Federation of European Biochemical Societies (FEBS) to attend the FEBB Practical Course on Protein interaction modules. Split, Croatia.
2007 – FCT PhD Fellowship

Awards to Cytoskeleton in Development and Disease Lab Students: