Drosophila Mon1 constitutes a novel node in the brain-gonad axis that is essential for female germline maturation

Development. 2019 Jul 10;146(13):dev166504. doi: 10.1242/dev.166504.


Monensin-sensitive 1 (Mon1) is an endocytic regulator that participates in the conversion of Rab5-positive early endosomes to Rab7-positive late endosomes. In Drosophila, loss of mon1 leads to sterility as the mon1 mutant females have extremely small ovaries with complete absence of late stage egg chambers - a phenotype reminiscent of mutations in the insulin pathway genes. Here, we show that expression of many Drosophila insulin-like peptides (ILPs) is reduced in mon1 mutants and feeding mon1 adults an insulin-rich diet can rescue the ovarian defects. Surprisingly, however, mon1 functions in the tyramine/octopaminergic neurons (OPNs) and not in the ovaries or the insulin-producing cells (IPCs). Consistently, knockdown of mon1 in only the OPNs is sufficient to mimic the ovarian phenotype, while expression of the gene in the OPNs alone can 'rescue' the mutant defect. Last, we have identified ilp3 and ilp5 as critical targets of mon1. This study thus identifies mon1 as a novel molecular player in the brain-gonad axis and underscores the significance of inter-organ systemic communication during development.

Keywords: Drosophila oogenesis; Insulin production; Inter-organ communication; Neuronal control.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain / metabolism*
  • Cell Differentiation / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Female
  • Gene Expression Regulation, Developmental
  • Germ Cells / physiology*
  • Gonads / metabolism*
  • Infertility, Female / genetics
  • Infertility, Female / pathology
  • Insulin / physiology
  • Insulins / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Oocytes / physiology
  • Oogenesis / genetics
  • Organ Size / genetics
  • Ovary / abnormalities
  • Ovary / growth & development*
  • Ovary / metabolism
  • Ovary / pathology
  • Ovum / physiology
  • Paracrine Communication / genetics
  • Signal Transduction / genetics


  • Drosophila Proteins
  • ILP3 protein, Drosophila
  • Ilp5 protein, Drosophila
  • Insulin
  • Insulins
  • Intercellular Signaling Peptides and Proteins
  • Mon1 protein, Drosophila