Analysis of Yorkie activity in scribble mutant cells challenged with different cell competitive environments. Indrayani Waghmare¹, Shilpi Verghese¹, Alyssa Lesko^2,3, Amit Singh^1,4,5, Madhuri Kango-Singh^1,4,5. 1) Department of Biology, University of Dayton, Dayton, OH; 2) University of Dayton Honors Program, Dayton, OH; 3) Department of Chemistry, University of Dayton, Dayton, OH; 4) Pre Medical Program, University of Dayton, Dayton, OH; 5) Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, OH.

   The Hippo pathway is responsible for regulating organ size through regulating the expression of a diverse array of target genes, and is conserved from flies to humans. Recent studies suggest a role fro Hippo signaling in maintaining tissue homeostasis and cell-cell interactions. scribble (scrib) is a neoplastic tumor suppressor gene that regulates growth and maintains apical-basal polarity. scrib acts downstream of Fat to regulate Warts activity in the Hippo pathway. Loss of function of scrib shows distinct phenotypes of survival and growth depending on the genetic background making it ideal to study local cell-cell interactions. Somatic clones of scrib^-/- cells face cell-competition through JNK mediated apoptosis. We studied somatic clones of scrib^-/- in various competitive backgrounds that improved survival (over expression of P35, Hippo pathway loss of function, Ras gain of function) or reduced growth rate of the surrounding cells (Minute/+). We found that additional mutations in scrib^-/- cells caused them to behave like super-competitors. Further, we found that the super-competitive trait is coupled with regulation of Hippo pathway target genes. We hypothesize that the different growth phenotypes are generated by local cell-cell interactions due to differential regulation of Yki activity levels between the mutant clone and the surrounding wild-type cells. To test this hypothesis we have studied the Yki mediated regulation of target genes during super-competition. We have also tested the requirement of differential Yki activity in the growth response of the mutant cells. Our results suggest that Yki activity levels determine the nature of competitive interaction.