Ph.D. Program in Biomedical Sciences and Oncology

Contatti

Supervisore

Tesi di dottorato

"A Novel FLVCR (Feline Leucemia Virus Subgroup C Receptor) isoform able to support Erythropoiesis”.

Nella tesi di laurea e' stato trattato il ruolo dell' esportatore di eme, FLVCR, coinvolto nella corretta formazione della vasculogenesi. Nel nostro laboratorio e' infatti presente un modello KO di topo, privo della proteina FLVCR. La sua assenza causa letalita' embrionale e difetti a livello dell' endotelio, che provocano gravi emorragie che si sviluppano inizialmente sulla punta delle zampe dell' embrione e successivamente su resto del corpo e la successiva comparsa di edema a livello della testa, probabilmente in conseguenza alle gravi emorragie. Analisi piu' approfondite di immunoistochimica sull' endotelio dimostrano una grave compromissione del tessuto che causerebbe l' emorragia e di conseguenza la morte dell' embrione.

Attività di ricerca

Partecipazione a congressi:

-         FEBS, 25 – 30 June 2011, Turin, Italy

-         European Zebrafish Meeting, 5-9 July 2011, Edimburgh, Scotland

-         Joint National Ph.D. Meeting -  ABCD, 20–22 October 2011, Gubbio Italy

Abstract:

Skeletal abnormalities and vessel defects in zebrafish deficient for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR)

Sonia Mercurio, Irma Zuni Bassi, Floriana Francalanci, Elisa De Luca, Deborah Chiabrando, Lorenzo Silengo, Fiorella Altruda, Massimo Santoro, Emanuela Tolosano.

 Department of Genetics, Biology and Biochemistry and Molecular Biotechnology Center, University of Turin, Turin, Italy.

Feline Leukemia Virus subgroup C receptor 1 (FLVCR1), a member of the major facilitator superfamily of transporter proteins, is a heme exporter reported to have a crucial role in erythropoiesis and cellular heme detoxification. We have recently generated FLVCR1 knock-out mice. These animals died at midgestion between E15.5-18.5 due to extended hemorrhages visible in the limbs, head and throughout the body wall. FLVCR1 KO embryos displayed vascular defects, likely responsible for hemorrhages, edema and skeletal abnormalities, but have normal erythropoiesis. To further address the role of FLVCR1 during development we knocked-down its expression in zebrafish with two different antisense morpholino oligonucleotides (MO) interfering with the translation or the splicing of the transcript. FLVCR1 morphants died within 5 days postfertilization. The morphants showed extended hemorrhages, severe vascular abnormalities and craniofacial cartilage malformations. Vascular defects are characterized by abnormal branching and formation of intersegmental vessels. Preliminary data showed that markers of erythroid differentiation were correctly expressed in FLVCR1 morphants suggesting that erythropoiesis is normal. These data demonstrate a crucial and conserved role for FLVCR in skeletal formation and highlight a previously unappreciated function for this protein in the development of blood vessels and maintenance of vascular integrity.