Cell Growth and Differentiation
Research Overview
Our group investigates the regulation of cellular properties by transcriptional and signaling networks during organogenesis. The intricate coordination of these processes requires the use of in vivo contexts to characterize key genes and genetic networks. To this end, we use the fruit fly (Drosophila melanogaster) as a highly versatile and genetically tractable model organism.
Developmental Signaling and Cellular Crosstalk
Our research aims to decipher the molecular mechanisms by which distinct cell types co-develop to form functional organs. Current objectives include:
- Signaling and Regulation: Investigating novel mechanisms within key signaling pathways, specifically the TGFβ/BMP pathway (including BMP2-regulated apoptosis) and the Myc oncogene, in collaboration with Dr. Fernando Casares (CABD, Seville) and Dr. Tiago Cordeiro (ITQB, Lisbon).
- Cellular Crosstalk: Characterizing the complex bidirectional communication between dynamic photoreceptor differentiation and retinal glia migration and polyploidization.
Disease Modeling and Cancer Research
We use Drosophila as a functional genomics platform to investigate the fundamental aspects of human cancer. In collaboration with Dr. Carla Oliveira (Expression Regulation in Cancer group, i3S), we have established a fly model to study Hereditary Diffuse Gastric Cancer (HDGC). Our work focuses on the functional impact of CTNNA1 germline variants to improve disease classification and clinical management. We are currently expanding this model to gain deeper insights into the underlying molecular mechanisms of the disease.
Retinal glial cells (in red) overmigrating in response to reduced fitness of neuronal progenitors.
Team
Renata Freitas
Collaborator
Selected Publications
Lobo S., Dias A., Pedro A.M., Ferreira M., Pinto-Oliveira A., São José C., Herrera-Mullar J., Pinto N., Colas C., Hüneburg R., Nattermann J., Boussemart L., Van Hest L.P., Moreira L., Horton C., Farengo Clark D., Tinschert S., Golmard L., Spier I., López-Fernández A., Oliveira D., Svrcek M., Bourgoin P., Coulet F., Delhomelle H., Davis J., Zäncker B., Lazaro C., Guerra J., Almeida M.L., Carrera S., Patiño A., Gundlach P., Laszkowska M., Strong V.E., Teixeira M.R., Schrader I., Steinke-Lange V., Gullo I., Sousa S., Batista M., Aretz S., Balmaña J., Aronson M., Antoniazzi A.P., Palmero E.I., Mansfield P., Van der Kolk L.E., Cats A., Van Dieren J.M., Castellví-Bel S., Katona B., Karam R., Pereira P.S., Benusiglio P.R., Oliveira C.
Hereditary diffuse gastric cancer spectrum associated with germline CTNNA1 loss of function revealed by clinical and molecular data from 351 carrier families and over 37 000 non-carrier controls. Gut:, 2025. [Journal: Article] [CI: 1] [IF: 25.8 (*)]
DOI: 10.1136/gutjnl-2024-334601 SCOPUS: 105019610466
Teixeira V., Singh K., Gama J.B., Moreira M., Celestino R., Xavier Carvalho A., Pereira P.S., Abreu C.M.C., Dantas T.J., Carter A.P., Gassmann R.
CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization. Journal of Cell Biology224(9):, 2025. [Journal: Article] [CI: 1] [IF: 6.4 (*)]
DOI: 10.1083/jcb.202411034 SCOPUS: 105010975079
Navarro T., Iannini A., Neto M., Campoy-Lopez A., Muñoz-García J., Pereira P.S., Ares S., Casares F.
Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in the Drosophila eye. PLoS Biology22(1):, 2024. [Journal: Article] [CI: 5] [IF: 7.2]
DOI: 10.1371/journal.pbio.3002450 SCOPUS: 85183785216
Tavares L., Grácio P., Ramos R., Traquete R., Relvas J.B., Pereira P.S.
The Pebble/Rho1/Anillin pathway controls polyploidization and axonal wrapping activity in the glial cells of the Drosophila eye. Developmental Biology473:90-96, 2021. [Journal: Article] [CI: 1] [IF: 3,1]
DOI: 10.1016/j.ydbio.2021.02.002 SCOPUS: 85101016149
Pinho M., Macedo J.C., Logarinho E., Pereira P.S.
NoL12 repression induces nucleolar stress-driven cellular senescence and is associated with normative aging. Molecular and Cellular Biology39(12):, 2019. [Journal: Article] [CI: 15] [IF: 3,6]
DOI: 10.1128/MCB.00099-19 SCOPUS: 85066485467
García-Morales D., Navarro T., Iannini A., Pereira P.S., Míguez D.G., Casares F.
Dynamic Hh signalling can generate temporal information during tissue patterning. Development146(8):, 2019. [Journal: Article] [CI: 7] [IF: 5,6]
DOI: 10.1242/dev.176933 SCOPUS: 85065344120
Eusebio N., Tavares L., Pereira P.
CtBP represses Dpp-dependent Mad activation during Drosophila eye development. Developmental Biology442(1):188-198, 2018. [Journal: Article] [CI: 6] [IF: 2,9]
DOI: 10.1016/j.ydbio.2018.07.018 SCOPUS: 85050401082
Tavares L., Correia A., Santos M.A., Relvas J.B., Pereira P.S.
dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation. PLoS Genetics13(3):, 2017. [Journal: Article] [CI: 8] [IF: 5,5]
DOI: 10.1371/journal.pgen.1006647 SCOPUS: 85016620416
Martins T., Eusebio N., Correia A., Marinho J., Casares F., Pereira P.S.
TGFβ/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands. Open Biology7(1):, 2017. [Journal: Article] [CI: 12] [IF: 3,3]
DOI: 10.1098/rsob.160258 SCOPUS: 85012931855
Neto M., Naval-Sánchez M., Potier D., Pereira P.S., Geerts D., Aerts S., Casares F.
Nuclear receptors connect progenitor transcription factors to cell cycle control. Scientific Reports7(1):, 2017. [Journal: Article] [CI: 12] [IF: 4,1]
DOI: 10.1038/s41598-017-04936-7 SCOPUS: 85021927654
Tavares L., Pereira E., Correia A., Santos M.A., Amaral N., Martins T., Relvas J.B., Pereira P.S.
Drosophila PS2 and PS3 integrins play distinct roles in retinal photoreceptors-glia interactions. GLIA63(7):1155-1165, 2015. [Journal: Article] [CI: 11] [IF: 6]
DOI: 10.1002/glia.22806 SCOPUS: 84928206519
Marinho J., Martins T., Neto M., Casares F., Pereira P.S.
The nucleolar protein Viriato/Nol12 is required for the growth and differentiation progression activities of the Dpp pathway during Drosophila eye development. Developmental Biology377(1):154-165, 2013. [Journal: Article] [CI: 15] [IF: 3,6]
DOI: 10.1016/j.ydbio.2013.02.003 SCOPUS: 84876321493
Freitas R., Gómez-Marín C., Wilson J.M., Casares F., Gómez-Skarmeta J.L.
Hoxd13 Contribution to the Evolution of Vertebrate Appendages. Developmental Cell23(6):1219-1229, 2012. [Journal: Article] [CI: 80] [IF: 12,9]
DOI: 10.1016/j.devcel.2012.10.015 SCOPUS: 84870845601
Caldeira J., Simões-Correia J., Paredes J., Pinto M.T., Sousa S., Corso G., Marrelli D., Roviello F., Pereira P.S., Weil D., Oliveira C., Casares F., Seruca R.
CPEB1, a novel gene silenced in gastric cancer: A Drosophila approach. Gut61(8):1115-1123, 2012. [Journal: Article] [CI: 44] [IF: 10,7]
DOI: 10.1136/gutjnl-2011-300427 SCOPUS: 84863719147
Martin D., Pantoja C., Fernández-Miñán A., Valdes-Quezada C., Moltó E., Matesanz F., Bogdanović O., De La Calle-Mustienes E., Domínguez O., Taher L., Furlan-Magaril M., Alcina A., Cañóon S., Fedetz M., Blasco M.A., Pereira P.S., Ovcharenko I., Recillas-Targa F., Montoliu L., Manzanares M., Guiǵo R., Serrano M., Casares F., Gómez-Skarmeta J.L.
Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes. Nature Structural and Molecular Biology18(6):708-714, 2011. [Journal: Article] [CI: 78] [IF: 12,7]
DOI: 10.1038/nsmb.2059 SCOPUS: 79958834622
Marinho J., Casares F., Pereira P.S.
The Drosophila Nol12 homologue viriato is a dMyc target that regulates nucleolar architecture and is required for dMyc-stimulated cell growth. Development138(2):349-357, 2011. [Journal: Article] [CI: 21] [IF: 6,6]
DOI: 10.1242/dev.054411 SCOPUS: 78751553525
Freitas R., Zhang G.J., Cohn M.J.
Evidence that mechanisms of fin development evolved in the midline of early vertebrates. Nature442(7106):1033-1037, 2006. [Journal: Article] [CI: 180] [IF: 26,7]
DOI: 10.1038/nature04984 SCOPUS: 33748305741
Pereira P.S., Teixeira A., Pinho S., Ferreira P., Fernandes J., Oliveira C., Seruca R., Suriano G., Casares F.
E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia. Human Molecular Genetics15(10):1704-1712, 2006. [Journal: Article] [CI: 32] [IF: 8,1]
DOI: 10.1093/hmg/ddl093 SCOPUS: 33745184835
Freitas R., Cohn M.J.
Genomic regulation of Hox collinearity. Developmental Cell10(1):8-9, 2006. [Journal: Short Survey] [CI: 3] [IF: 13,5]
DOI: 10.1016/j.devcel.2005.12.008 SCOPUS: 29744445744
Costas J., Pereira P.S., Vieira C.P., Pinho S., Vieira J., Casares F.
Dynamics and function of intron sequences of the wingless gene during the evolution of the Drosophila genus. Evolution and Development6(5):325-335, 2004. [Journal: Article] [CI: 7] [IF: 2,7]
DOI: 10.1111/j.1525-142X.2004.04040.x SCOPUS: 4644220375
Hereditary diffuse gastric cancer spectrum associated with germline CTNNA1 loss of function revealed by clinical and molecular data from 351 carrier families and over 37 000 non-carrier controls. Gut:, 2025. [Journal: Article] [CI: 1] [IF: 25.8 (*)]
DOI: 10.1136/gutjnl-2024-334601 SCOPUS: 105019610466
Teixeira V., Singh K., Gama J.B., Moreira M., Celestino R., Xavier Carvalho A., Pereira P.S., Abreu C.M.C., Dantas T.J., Carter A.P., Gassmann R.
CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization. Journal of Cell Biology224(9):, 2025. [Journal: Article] [CI: 1] [IF: 6.4 (*)]
DOI: 10.1083/jcb.202411034 SCOPUS: 105010975079
Navarro T., Iannini A., Neto M., Campoy-Lopez A., Muñoz-García J., Pereira P.S., Ares S., Casares F.
Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in the Drosophila eye. PLoS Biology22(1):, 2024. [Journal: Article] [CI: 5] [IF: 7.2]
DOI: 10.1371/journal.pbio.3002450 SCOPUS: 85183785216
Tavares L., Grácio P., Ramos R., Traquete R., Relvas J.B., Pereira P.S.
The Pebble/Rho1/Anillin pathway controls polyploidization and axonal wrapping activity in the glial cells of the Drosophila eye. Developmental Biology473:90-96, 2021. [Journal: Article] [CI: 1] [IF: 3,1]
DOI: 10.1016/j.ydbio.2021.02.002 SCOPUS: 85101016149
Pinho M., Macedo J.C., Logarinho E., Pereira P.S.
NoL12 repression induces nucleolar stress-driven cellular senescence and is associated with normative aging. Molecular and Cellular Biology39(12):, 2019. [Journal: Article] [CI: 15] [IF: 3,6]
DOI: 10.1128/MCB.00099-19 SCOPUS: 85066485467
García-Morales D., Navarro T., Iannini A., Pereira P.S., Míguez D.G., Casares F.
Dynamic Hh signalling can generate temporal information during tissue patterning. Development146(8):, 2019. [Journal: Article] [CI: 7] [IF: 5,6]
DOI: 10.1242/dev.176933 SCOPUS: 85065344120
Eusebio N., Tavares L., Pereira P.
CtBP represses Dpp-dependent Mad activation during Drosophila eye development. Developmental Biology442(1):188-198, 2018. [Journal: Article] [CI: 6] [IF: 2,9]
DOI: 10.1016/j.ydbio.2018.07.018 SCOPUS: 85050401082
Tavares L., Correia A., Santos M.A., Relvas J.B., Pereira P.S.
dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation. PLoS Genetics13(3):, 2017. [Journal: Article] [CI: 8] [IF: 5,5]
DOI: 10.1371/journal.pgen.1006647 SCOPUS: 85016620416
Martins T., Eusebio N., Correia A., Marinho J., Casares F., Pereira P.S.
TGFβ/Activin signalling is required for ribosome biogenesis and cell growth in Drosophila salivary glands. Open Biology7(1):, 2017. [Journal: Article] [CI: 12] [IF: 3,3]
DOI: 10.1098/rsob.160258 SCOPUS: 85012931855
Neto M., Naval-Sánchez M., Potier D., Pereira P.S., Geerts D., Aerts S., Casares F.
Nuclear receptors connect progenitor transcription factors to cell cycle control. Scientific Reports7(1):, 2017. [Journal: Article] [CI: 12] [IF: 4,1]
DOI: 10.1038/s41598-017-04936-7 SCOPUS: 85021927654
Tavares L., Pereira E., Correia A., Santos M.A., Amaral N., Martins T., Relvas J.B., Pereira P.S.
Drosophila PS2 and PS3 integrins play distinct roles in retinal photoreceptors-glia interactions. GLIA63(7):1155-1165, 2015. [Journal: Article] [CI: 11] [IF: 6]
DOI: 10.1002/glia.22806 SCOPUS: 84928206519
Marinho J., Martins T., Neto M., Casares F., Pereira P.S.
The nucleolar protein Viriato/Nol12 is required for the growth and differentiation progression activities of the Dpp pathway during Drosophila eye development. Developmental Biology377(1):154-165, 2013. [Journal: Article] [CI: 15] [IF: 3,6]
DOI: 10.1016/j.ydbio.2013.02.003 SCOPUS: 84876321493
Freitas R., Gómez-Marín C., Wilson J.M., Casares F., Gómez-Skarmeta J.L.
Hoxd13 Contribution to the Evolution of Vertebrate Appendages. Developmental Cell23(6):1219-1229, 2012. [Journal: Article] [CI: 80] [IF: 12,9]
DOI: 10.1016/j.devcel.2012.10.015 SCOPUS: 84870845601
Caldeira J., Simões-Correia J., Paredes J., Pinto M.T., Sousa S., Corso G., Marrelli D., Roviello F., Pereira P.S., Weil D., Oliveira C., Casares F., Seruca R.
CPEB1, a novel gene silenced in gastric cancer: A Drosophila approach. Gut61(8):1115-1123, 2012. [Journal: Article] [CI: 44] [IF: 10,7]
DOI: 10.1136/gutjnl-2011-300427 SCOPUS: 84863719147
Martin D., Pantoja C., Fernández-Miñán A., Valdes-Quezada C., Moltó E., Matesanz F., Bogdanović O., De La Calle-Mustienes E., Domínguez O., Taher L., Furlan-Magaril M., Alcina A., Cañóon S., Fedetz M., Blasco M.A., Pereira P.S., Ovcharenko I., Recillas-Targa F., Montoliu L., Manzanares M., Guiǵo R., Serrano M., Casares F., Gómez-Skarmeta J.L.
Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes. Nature Structural and Molecular Biology18(6):708-714, 2011. [Journal: Article] [CI: 78] [IF: 12,7]
DOI: 10.1038/nsmb.2059 SCOPUS: 79958834622
Marinho J., Casares F., Pereira P.S.
The Drosophila Nol12 homologue viriato is a dMyc target that regulates nucleolar architecture and is required for dMyc-stimulated cell growth. Development138(2):349-357, 2011. [Journal: Article] [CI: 21] [IF: 6,6]
DOI: 10.1242/dev.054411 SCOPUS: 78751553525
Freitas R., Zhang G.J., Cohn M.J.
Evidence that mechanisms of fin development evolved in the midline of early vertebrates. Nature442(7106):1033-1037, 2006. [Journal: Article] [CI: 180] [IF: 26,7]
DOI: 10.1038/nature04984 SCOPUS: 33748305741
Pereira P.S., Teixeira A., Pinho S., Ferreira P., Fernandes J., Oliveira C., Seruca R., Suriano G., Casares F.
E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia. Human Molecular Genetics15(10):1704-1712, 2006. [Journal: Article] [CI: 32] [IF: 8,1]
DOI: 10.1093/hmg/ddl093 SCOPUS: 33745184835
Freitas R., Cohn M.J.
Genomic regulation of Hox collinearity. Developmental Cell10(1):8-9, 2006. [Journal: Short Survey] [CI: 3] [IF: 13,5]
DOI: 10.1016/j.devcel.2005.12.008 SCOPUS: 29744445744
Costas J., Pereira P.S., Vieira C.P., Pinho S., Vieira J., Casares F.
Dynamics and function of intron sequences of the wingless gene during the evolution of the Drosophila genus. Evolution and Development6(5):325-335, 2004. [Journal: Article] [CI: 7] [IF: 2,7]
DOI: 10.1111/j.1525-142X.2004.04040.x SCOPUS: 4644220375
