The main focus of our laboratory is clarifying the roles of DNA binding proteins belonging to the HMG box superfamily during embryonic development. In particular, I studied Sox18 and Sox7 in zebrafish and our data show that they act redundantly in vascular development. Mutations in SOX18 have been associated with Hypotrichosis-Lymphedema-Telangiectasia (HLT), a human syndrome combining defects in hair follicle, blood and lymphatic vessels development. Similarly, spontaneous mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice, including symptoms of lymphatic dysfunction. On the other hand, mice null for Sox18 display only mild coat defects. This suggests that other Sox proteins may compensate for the absence of Sox18. zfsox18 and zfsox7 genes are co-expressed in endothelial cells and their precursors. Knock down of either genes had minimal effects on blood vessels, however their simultaneous knockdown selectively affects trunk/tail blood circulation: endothelial cells that fail to acquire the proper arteriovenous identity and multiple fusions are present between the major axial vessels. To identify the hypothetical targets of sox18 and sox7 I performed a genome wide analysis using Affymetrix chip. We compared the expression of control embryos and double knockdown at two different time points: during initial steps of blood vessels formation and around the time when circulation begins. Functional studies of the most interesting identified genes will follow.
|Titolo:||Sox18 and Sox7 play redundant roles in endothelial cell differentiation|
|Relatore:||BELTRAME, MONICA DANIELA|
|Supervisori e coordinatori interni:||MANTOVANI, ROBERTO|
|Data di pubblicazione:||2008|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Citazione:||Sox18 and Sox7 play redundant roles in endothelial cell differentiation ; M. Beltrame, R. Mantovani. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2008. ((20. ciclo, Anno Accademico 2007/2008.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|