Loredana Marcia
Technician
Area of interest:
I have many years of expertise and experience in molecular and cell biology, developmental biology, gene regulation and expression, maintenance and characterization of mouse models. I have been working on the functional characterization of the FOXL2 and CRLF1 proteins, involved respectively in the Blepharophimosisi/Ptosis/Epicanthus inversus (BPES) and the Crisponi/CISS1 (CS/CISS1) syndromes and on the phenotypic characterization of a Foxl2 knockout mouse, a model for human BPES, to understand the physiopathological mechanisms underlying female fertility and skeletal development.
My main skill is in immune-histochemistry analysis in eukaryotic cells and murine tissues, covering tissue collection and sample preparation, immunohistochemical staining and visualization by bright field, immunofluorescence, and confocal microscopy.
Most significant publications:
2018
Angius, A.; Uva, P.; Buers, I.; Oppo, M.; Puddu, A.; Onano, S.; Persico, I.; Loi, A.; Marcia, L.; H?hne, W.; Cuccuru, G.; Fotia, G.; Deiana, M.; Marongiu, M.; Atalay, H. T.; Inan, S.; El Assy, O.; Smit, L. M. E.; Okur, I.; Boduroglu, K.; Utine, G. E.; Kılıç, E.; Zampino, G.; Crisponi, G.; Crisponi, L.; Rutsch, F.
Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa. Journal Article
In: 102 (4), pp. 713, 2018.
@article{pmid29625027,
title = {Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa.},
author = {Angius, A. and Uva, P. and Buers, I. and Oppo, M. and Puddu, A. and Onano, S. and Persico, I. and Loi, A. and Marcia, L. and H?hne, W. and Cuccuru, G. and Fotia, G. and Deiana, M. and Marongiu, M. and Atalay, H. T. and Inan, S. and El Assy, O. and Smit, L. M. E. and Okur, I. and Boduroglu, K. and Utine, G. E. and Kılıç, E. and Zampino, G. and Crisponi, G. and Crisponi, L. and Rutsch, F. },
year = {2018},
date = {2018-01-01},
volume = {102},
number = {4},
pages = {713},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2016
Marongiu, Mara; Deiana, Manila; Marcia, Loredana; Sbardellati, Andrea; Asunis, Isadora; Meloni, Alessandra; Angius, Andrea; Cusano, Roberto; Loi, Angela; Crobu, Francesca; Fotia, Giorgio; Cucca, Francesco; Schlessinger, David; Crisponi, Laura
Novel action of FOXL2 as mediator of Col1a2 gene autoregulation Journal Article
In: Developmental Biology, 416 (1), pp. 200–211, 2016, ISSN: 1095-564X.
@article{marongiu_novel_2016,
title = {Novel action of FOXL2 as mediator of Col1a2 gene autoregulation},
author = {Mara Marongiu and Manila Deiana and Loredana Marcia and Andrea Sbardellati and Isadora Asunis and Alessandra Meloni and Andrea Angius and Roberto Cusano and Angela Loi and Francesca Crobu and Giorgio Fotia and Francesco Cucca and David Schlessinger and Laura Crisponi},
doi = {10.1016/j.ydbio.2016.05.022},
issn = {1095-564X},
year = {2016},
date = {2016-08-01},
journal = {Developmental Biology},
volume = {416},
number = {1},
pages = {200--211},
abstract = {FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause.
2015
Marongiu, Mara; Marcia, Loredana; Pelosi, Emanuele; Lovicu, Mario; Deiana, Manila; Zhang, Yonqing; Puddu, Alessandro; Loi, Angela; Uda, Manuela; Forabosco, Antonino; Schlessinger, David; Crisponi, Laura
FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice Journal Article
In: BMC developmental biology, 15 , pp. 27, 2015, ISSN: 1471-213X.
@article{marongiu_foxl2_2015,
title = {FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice},
author = {Mara Marongiu and Loredana Marcia and Emanuele Pelosi and Mario Lovicu and Manila Deiana and Yonqing Zhang and Alessandro Puddu and Angela Loi and Manuela Uda and Antonino Forabosco and David Schlessinger and Laura Crisponi},
doi = {10.1186/s12861-015-0072-y},
issn = {1471-213X},
year = {2015},
date = {2015-07-01},
journal = {BMC developmental biology},
volume = {15},
pages = {27},
abstract = {BACKGROUND: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation.
METHODS: Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.
RESULTS: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus.
CONCLUSIONS: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation.
METHODS: Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.
RESULTS: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus.
CONCLUSIONS: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.
METHODS: Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.
RESULTS: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus.
CONCLUSIONS: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.
2010
Marongiu, M.; Deiana, M.; Meloni, A.; Marcia, L.; Puddu, A.; Cao, A.; Schlessinger, D.; Crisponi, L.
The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity Journal Article
In: PLoS One, 5 (3), pp. e9477, 2010.
@article{pmid20209145,
title = {The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity},
author = {Marongiu, M. and Deiana, M. and Meloni, A. and Marcia, L. and Puddu, A. and Cao, A. and Schlessinger, D. and Crisponi, L.},
year = {2010},
date = {2010-03-01},
journal = {PLoS One},
volume = {5},
number = {3},
pages = {e9477},
abstract = {The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.
- Monserrato
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