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.
