Hindsight mediates the role of notch in suppressing hedgehog signaling and cell proliferation

Dev Cell. 2007 Mar;12(3):431-42. doi: 10.1016/j.devcel.2007.02.003.

Abstract

Temporal and spatial regulation of proliferation and differentiation by signaling pathways is essential for animal development. Drosophila follicular epithelial cells provide an excellent model system for the study of temporal regulation of cell proliferation. In follicle cells, the Notch pathway stops proliferation and promotes a switch from the mitotic cycle to the endocycle. Here, we show that zinc-finger transcription factor Hindsight mediates the role of Notch in regulating cell differentiation and the switch of cell-cycle programs. Hindsight is required and sufficient to stop proliferation and induce the transition to the endocycle. To do so, it represses string, Cut, and Hedgehog signaling, which promote proliferation during early oogenesis. Hindsight, along with another zinc-finger protein, Tramtrack, downregulates Hedgehog signaling through transcriptional repression of cubitus interruptus. Our studies suggest that Hindsight bridges the two antagonistic pathways, Notch and Hedgehog, in the temporal regulation of follicle-cell proliferation and differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Embryonic Development / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / embryology
  • Ovarian Follicle / metabolism
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Transcription Factors
  • ci protein, Drosophila
  • ct protein, Drosophila
  • peb protein, Drosophila
  • ttk protein, Drosophila
  • Protein Tyrosine Phosphatases
  • stg protein, Drosophila