MSc Exit Seminar – Parama Talukder (Tepass Lab)

Crumbs (Crb) is an apical determinant, which is not only required for maintaining the apical membrane identity during embryogenesis, but surprisingly also causes neoplastic overgrowth when overexpressed in imaginal disc epithelia. My work further characterized the Crb-induced overgrowth in imaginal wing discs. I showed that both the conserved binding sites within the Crb cytoplasmic tail, a FERM-domain binding motif (FDB) and a PDZ-domain binding motif (PDB) contribute to the Crb-induced neoplastic phenotype. Downstream of Crb overexpression, the JAK/STAT proliferative pathway, and excessive division in general are required for mediating not only the excess tissue growth but also the loss of epithelial integrity, a key feature of the neoplastic phenotype. Finally, my work confirmed that Crb overexpression activates the JNK signaling pathway and uncovered a novel role of Crb overexpression levels in eliciting distinct JNK signaling responses. Moderate Crb overexpression levels cause JNK-dependent overproliferation as was anticipated based on previous findings. In contrast, high levels of Crb overexpression had JNK-dependent pro-apoptotic activity. These findings reveal Crb as a unique tumour oncogene among polarity factors, and open avenues for further investigations into Crb ability to direct downstream proliferative or apoptotic responses. 

https://us02web.zoom.us/j/88026443768