title: The Hippo pathway controls border cell migration through distinct mechanisms in outer border cells and polar cells of the Drosophila ovary.
abstract: The Hippo pathway is a key signaling cascade in controlling organ size. The core components of this pathway are two kinases, Hippo (Hpo) and Warts (Wts), and a transcriptional coactivator, Yorkie (Yki). Yes-associated protein (YAP, a Yki homolog in mammals) promotes epithelial-mesenchymal transition and cell migration in vitro. Here, we use border cells in the Drosophila ovary as a model to study Hippo pathway functions in cell migration in vivo. During oogenesis, polar cells secrete Unpaired (Upd), which activates JAK/STAT signaling of neighboring cells and specifies them into outer border cells. The outer border cells form a cluster with polar cells and undergo migration. We find that hpo and wts are required for migration of the border cell cluster. In outer border cells, overexpression of hpo disrupts polarization of the actin cytoskeleton and attenuates migration. In polar cells, knockdown of hpo and wts or overexpression of yki impairs border cell induction and disrupts migration. These manipulations in polar cells reduce JAK/STAT activity in outer border cells. Expression of upd-lacZ is increased and decreased in yki and hpo mutant polar cells, respectively. Furthermore, forced expression of upd in polar cells rescues defects of border cell induction and migration caused by wts knockdown. These results suggest that Yki negatively regulates border cell induction by inhibiting JAK/STAT signaling. Together, our data elucidate two distinct mechanisms of the Hippo pathway in controlling border cell migration: (1) in outer border cells, it regulates polarized distribution of the actin cytoskeleton; (2) in polar cells, it regulates upd expression to control border cell induction and migration.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Tzu-Huai
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Yeh
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Tsu-Wei
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan jyyu@ym.edu.tw.
authors.forename: Jenn-Yah
authors.initials: JY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D002452:Cell Count; D002465:Cell Movement; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008954:Models, Biological; D010053:Ovary / Q000166:cytology* / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D049452:Green Fluorescent Proteins; D053612:Janus Kinases
keywords: Drosophila; Hippo pathway; JAK/STAT; border cell migration; oogenesis