Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting neurodevelopment and the gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and 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, an intracellular pathway involved in regulation of expression of several genes controlling cell division and embryonic development. 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 cyclinD1 downregulation. Drosophila melanogaster is an inexpensive model to study CdLS and to screen in vivo for therapeutic compounds. Therefore, we have used flies 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. Moreover, we have selected D. melanogaster mutants to screen for chemicals that revert the CdLS associated-phenotypes efficiently. In particular, we have tested several WNT activators and differences in modulating CdLS phenotypes will be discussed.
Modulating the WNT pathway in Drosophila models of Cornelia de Lange Syndrome / P. Grazioli, A. Selicorni, C. Gervasini, T. Vaccari, V. Massa. ((Intervento presentato al 20. convegno SIGU tenutosi a Napoli nel 2017.
|Titolo:||Modulating the WNT pathway in Drosophila models of 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:||15-nov-2017|
|Parole Chiave:||Cornelia de Lange Syndrome; WNT pathway; Drosophila|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
Settore MED/03 - Genetica Medica
|Citazione:||Modulating the WNT pathway in Drosophila models of Cornelia de Lange Syndrome / P. Grazioli, A. Selicorni, C. Gervasini, T. Vaccari, V. Massa. ((Intervento presentato al 20. convegno SIGU tenutosi a Napoli nel 2017.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|