Neural tube is the embryonic precursor of brain and spinal cord, and forms as a consequence of closure of the developing neuroepithelium. If closure events fail, the embryo will manifest a neural tube defect (NTD: spina bifida or exencephaly). Despite significative advantage in the field, the elucidation of genetic factors associated to NTD has remained elusive and NTDs are the second most common congenital defects affecting human pregnancies. This project aims at investigating two different aspect of NTDs: on one side the analysis of the transcription factor Sax-1, that was found to be down-regulated in a microarray screening in the Kumba mouse (Zic2Ku) NTDs model. The expression of Sax-1 correlates remarkably closely with the progression of posterior closure of the neuroepithelium, overlapping with Zic2 expression. Functional studies of Sax1 and Zic2 in zebrafish will be flanked to mouse embryos and in vitro analyses. On the other side, this project investigates the role of miRNAs in neural tube development on human samples. From a database of 534 fetal autopsies, we selected 9 fetuses with NTDs (7 myelomeningocele, 2 anencephaly). Using a combination of bioinformatics tools (MirWalk, CO-ME-TA, DAVID), we have identified 4 candidate miRNAs whose predicted targets are significantly enriched for functional pathways related to neurulation. Moreover, a systematic analysis of all miRNAs expressed in NTDs is being performed using a Small RNA sequencing approach.
|Titolo:||Identification of genetic factors associated with neural tube defects|
|Data di pubblicazione:||2014|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Enti collegati al convegno:||European Society of Human Genetics (ESHG)|
|Citazione:||Identification of genetic factors associated with neural tube defects / V. Massa, G. Soldà, L. Avagliano, G. Fazio, G. Cazzaniga, G. Bulfamante, A. Marozzi, F. Cotelli, A. Pistocchi, A. Gallina. ((Intervento presentato al convegno European Human Genetics Conference tenutosi a Milano nel 2014.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|