TitleThe fat-hippo signaling network and regeneration
NameStaley, Binnaz Kucuk (author), Grant, Barth (chair), Steward, Ruth (internal member), Irvine, Ken (internal member), Soto, Martha (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectCell and Developmental Biology,
DescriptionThe Hippo (Hpo) and Fat (Ft) pathways form an interconnected signaling network, which has a crucial role in growth control and is conserved from flies to humans. The Fat/Hippo pathway regulates growth, gene expression and planar cell polarity (PCP) (asymmetry of a cell within the plane of the epithelium), independently from tissue patterning. The inhibition of the pathway results in overgrown organs while cell fate determination is not affected. An ever-increasing amount of research has shown the pathway’s role in many different biological processes, including cancer and regeneration. We identified a novel gene, lowfat (lft) as a modulator of the Ft signaling pathway. Lft is a conserved cytoplasmic protein that localizes to the sub-apical membranes of cells, where Ft and Dachsous (Ds), two members of the Ft pathway, are normally localized. Ft and Ds protein levels are reduced in lft mutant cells and increased in lft over-expressing cells. Lft can physically interact with the cytoplasmic domains of Ft and Ds, and regulates their levels post-transcriptionally. lft mutants display a characteristic Fat pathway phenotype in the wing that resembles weak mutant alleles of ft or ds. Furthermore, lft can genetically interact with both fat and ds, which results in more severe phenotypes. We discovered that, in addition to its crucial role in growth control, the Hippo pathway is also required during regenerative response upon damage induction. We used the Drosophila adult midgut, the equivalent of the mammalian small intestine, as our model organ. Homeostasis in the midgut is maintained by intestinal stem cells (ISCs). In response to cell loss caused by infection or expression of apoptotic proteins, ISCs increase the rate of cell proliferation. We showed that Yki, a transcriptional co-activator of the Ft/Hpo pathway, is activated in enterocytes (absorptive cells of the midgut) upon damage or activation of the damage-sensing Jnk pathway. This leads to a nonautonomous induction of ISC proliferation by regulation of the Jak/Stat pathway. Our data identifies a role for the Hippo pathway in regulating stem cell proliferation and intestinal regeneration upon damage.
NoteIncludes bibliographical references
Noteby Binnaz Kucuk Staley
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.