Hippo pathway and Bonus control developmental cell fate decisions in the Drosophila eye

Dev Cell. 2023 Mar 13;58(5):416-434.e12. doi: 10.1016/j.devcel.2023.02.005. Epub 2023 Mar 2.

Abstract

The canonical function of the Hippo signaling pathway is the regulation of organ growth. How this pathway controls cell-fate determination is less well understood. Here, we identify a function of the Hippo pathway in cell-fate decisions in the developing Drosophila eye, exerted through the interaction of Yorkie (Yki) with the transcriptional regulator Bonus (Bon), an ortholog of mammalian transcriptional intermediary factor 1/tripartite motif (TIF1/TRIM) family proteins. Instead of controlling tissue growth, Yki and Bon promote epidermal and antennal fates at the expense of the eye fate. Proteomic, transcriptomic, and genetic analyses reveal that Yki and Bon control these cell-fate decisions by recruiting transcriptional and post-transcriptional co-regulators and by repressing Notch target genes and activating epidermal differentiation genes. Our work expands the range of functions and regulatory mechanisms under Hippo pathway control.

Keywords: Bon; E(spl)-C; HDAC1; Notch; Su(var)2-10; Yki; cell fate; eye specification; protein interaction; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Drosophila* / metabolism
  • Gene Expression Regulation, Developmental
  • Hippo Signaling Pathway
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mammals / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteomics
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • Trans-Activators
  • Bon protein, Drosophila