Rudhira /BCAS3 regulates epithelial to mesenchymal transition during mammalian vascular development

Abstract

This thesis describes the functional role of BCAS3, a cytoskeletal protein that is essential for blood vessel formation. BCAS3 is the human ortholog of mouse Rudhira, which is expressed during embryonic vascular development and in normal and pathological angiogenesis. Genomic deletion of rudhira was earlier shown to cause mid-gestation lethality with severe vascular patterning defects. In this thesis, by transcriptome analysis of gene expression, we show that ablation of rudhira perturbs mediators of angiogenesis, adhesion, migration and matrix degradation as well as several components of the TGFβ signaling pathway. This suggests a role for cytoskeletal Rudhira in regulating TGFβ–mediated angiogenic processes. We also show that BCAS3 promotes the epithelial to mesenchymal transition (EMT) in vitro. Knockdown of BCAS3 delays the initiation of EMT, which affects cell migration. Using human embryonic stem cell differentiation as a model for human development we show that BCAS3 expression is concomitant with initiation of developmental EMT. Thus, we identify a functional role for a cytoskeletal effector that plays a critical role in development as well as tumor progression.