Variant cell cycles regulated by Notch signaling control cell size and ensure a functional blood-brain barrier

Development. 2018 Feb 13;145(3):dev157115. doi: 10.1242/dev.157115.

Abstract

Regulation of cell size is crucial in development. In plants and animals two cell cycle variants are employed to generate large cells by increased ploidy: the endocycle and endomitosis. The rationale behind the choice of which of these cycles is implemented is unknown. We show that in the Drosophila nervous system the subperineurial glia (SPG) are unique in using both the endocycle and endomitosis to grow. In the brain, the majority of SPG initially endocycle, then switch to endomitosis during larval development. The Notch signaling pathway and the String Cdc25 phosphatase are crucial for the endocycle versus endomitosis choice, providing the means experimentally to change cells from one to the other. This revealed fundamental insights into the control of cell size and the properties of endomitotic cells. Endomitotic cells attain a higher ploidy and larger size than endocycling cells, and endomitotic SPG are necessary for the blood-brain barrier. Decreased Notch signaling promotes endomitosis even in the ventral nerve cord SPG that normally are mononucleate, but not in the endocycling salivary gland cells, revealing tissue-specific cell cycle responses.

Keywords: Drosophila; Endocycle; Endomitosis; Polyploid; Salivary gland; Subperineurial glia.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blood-Brain Barrier / cytology*
  • Blood-Brain Barrier / growth & development
  • Blood-Brain Barrier / physiology*
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / physiology
  • Cell Size
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / physiology*
  • Larva / cytology
  • Larva / growth & development
  • Larva / physiology
  • Mitosis / genetics
  • Mitosis / physiology
  • Neuroglia / physiology
  • Ploidies
  • Protein Tyrosine Phosphatases / physiology
  • RNA Interference
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / genetics
  • Receptors, Notch / physiology*
  • Signal Transduction

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Protein Tyrosine Phosphatases
  • stg protein, Drosophila