Oral Presentation 2019 Hunter Cell Biology Meeting

Control of tissue growth and form via the Hippo pathway (#7)

Barry J Thompson 1
  1. John Curtin School of Medical Research, Acton, ACT, Australia

How animal tissues grow to the correct size and shape remains a fundamental unsolved problem in biology.  Powerful genetic screens in the fruit fly Drosophila have uncovered key genes required for tissues to achieve their correct size and shape, but how these genes function together during development remains a mystery.  A key example is the Hippo signalling pathway, whose genetic inactivation causes dramatic tissue overgrowth in Drosophila.  It is understood that the Hippo pathway functions by inhibiting the action of a key transcriptional co-activator named Yorkie (Yki) in Drosophila (or YAP/TAZ in mammals), which normally binds to the Scalloped (Sd) transcription factor (or TEAD1-4 in mammals) to induce target genes such as bantam and myc to drive cell proliferation.  However, it is still not understood how the Hippo pathway is physiologically regulated as tissues grow and then undergo morphogenetic change to achieve their final form.  We seek to examine whether and how the Hippo pathway is regulated by fundamental inputs such as animal nutrition (as animal growth requires nutrient intake), genetic programs that coordinate cell behaviour through intercellular communication (including morphogen gradients and their downstream gene regulatory networks), and tissue mechanics (as mechanical forces are instrumental to both growth and morphogenesis).  I will present new and unpublished data on the physiological regulation of Hippo signalling by these different inputs.