Introduction: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting neurodevelopment, gastrointestinal and musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, or HDAC8 genes. These genes codify for the cohesin complex, a multiprotein structure playing a role in chromatid adhesion, DNA repair and gene expression regulation. It has been demonstrated that a strong correlation exists between cohesin complex function and WNT signalling. Recently, it has been observed that chemical activation of the WNT pathway in nipblb-loss-of-function zebrafish embryos and in NIPBL-mutated patient fibroblasts rescued the adverse phenotype. Both embryos and fibroblasts present similar patterns of canonical WNT pathway alterations and CCND1 downregulation. Materials and Methods: Drosophila melanogaster is an inexpensive model to study CdLS and to screen in vivo for therapeutic compounds. Therefore, we have selected fly strains mutated in nipped-B and hdac3 genes (respectively NIPBL and HDAC8 in humans) for assessing the existing correlation between cohesin complex and WNT pathway and to screen for chemicals that revert the CdLS associated-phenotypes efficiently. Results: We have confirmed that mutated flies weight 5% less than wild type. Moreover, we have tested lithium chloride (LiCl) as WNT activator, demonstrating that 250mM is the highest concentration tolerated. Conclusions: Hence, we hypothesize that WNT pathway activation could improve mutant phenotype. We will be testing different doses of LiCl and other WNT activator to assess whether some of those chemical compounds could revert the syndrome-associated phenotype.
Drosophila melanogaster as a model to study WNT pathway alteration in Cornelia de Lange Syndrome / P. Grazioli, A. Selicorni, C.C.G. Gervasini, T. Vaccari, V. Massa. ((Intervento presentato al 52. convegno European Human Genetics Conference tenutosi a Milano nel 2018.
|Titolo:||Drosophila melanogaster as a model to study WNT pathway alteration in Cornelia de Lange Syndrome|
GRAZIOLI, PAOLO (Primo) [Writing – Original Draft Preparation] (Corresponding)
GERVASINI, CRISTINA COSTANZA GIOVANNA [Membro del Collaboration Group]
VACCARI, THOMAS [Membro del Collaboration Group]
MASSA, VALENTINA (Ultimo) [Writing – Review & Editing]
|Data di pubblicazione:||17-giu-2018|
|Parole Chiave:||Cornelia de Lange Syndrome; WNT pathway; Lithium chloride|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Citazione:||Drosophila melanogaster as a model to study WNT pathway alteration in Cornelia de Lange Syndrome / P. Grazioli, A. Selicorni, C.C.G. Gervasini, T. Vaccari, V. Massa. ((Intervento presentato al 52. convegno European Human Genetics Conference tenutosi a Milano nel 2018.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|