A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes

PLoS Genet. 2017 Jul 17;13(7):e1006910. doi: 10.1371/journal.pgen.1006910. eCollection 2017 Jul.

Abstract

Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells. Neighboring cells that receive the EGF signal initiate a largely unknown pathway to promote oenocyte fate. Here, we show that Abd-A also plays a cell autonomous role in inducing oenocyte fate by activating the expression of the Pointed-P1 (PntP1) ETS transcription factor downstream of EGF signaling. Genetic studies demonstrate that both PntP1 and PntP2 are required for oenocyte specification. Moreover, we found that PntP1 contains a conserved enhancer (PntP1OE) that is activated in oenocyte precursor cells by EGF signaling via direct regulation by the Pnt transcription factors as well as a transcription factor complex consisting of Abd-A, Extradenticle, and Homothorax. Our findings demonstrate that the same Abd-A Hox complex required for sending the EGF signal from SOP cells, enhances the competency of receiving cells to select oenocyte cell fate by up-regulating PntP1. Since PntP1 is a downstream effector of EGF signaling, these findings provide insight into how a Hox factor can both trigger and potentiate the EGF signal to promote an essential cell fate along the body plan.

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila / enzymology
  • Drosophila / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Gene Expression Regulation, Developmental
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Sense Organs / growth & development
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • pnt protein, Drosophila
  • Epidermal Growth Factor