A critical role for cyclin E in cell fate determination in the central nervous system of Drosophila melanogaster

Nat Cell Biol. 2005 Jan;7(1):56-62. doi: 10.1038/ncb1203. Epub 2004 Dec 5.

Abstract

We have examined the process by which cell diversity is generated in neuroblast (NB) lineages in the central nervous system of Drosophila melanogaster. Thoracic NB6-4 (NB6-4t) generates both neurons and glial cells, whereas NB6-4a generates only glial cells in abdominal segments. This is attributed to an asymmetric first division of NB6-4t, localizing prospero (pros) and glial cell missing (gcm) only to the glial precursor cell, and a symmetric division of NB6-4a, where both daughter cells express pros and gcm. Here we show that the NB6-4t lineage represents the ground state, which does not require the input of any homeotic gene, whereas the NB6-4a lineage is specified by the homeotic genes abd-A and Abd-B. They specify the NB6-4a lineage by down-regulating levels of the G1 cyclin, DmCycE (CycE). CycE, which is asymmetrically expressed after the first division of NB6-4t, functions upstream of pros and gcm to specify the neuronal sublineage. Loss of CycE function causes homeotic transformation of NB6-4t to NB6-4a, whereas ectopic CycE induces reverse transformations. However, other components of the cell cycle seem to have a minor role in this process, suggesting a critical role for CycE in regulating cell fate in segment-specific neural lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Central Nervous System / cytology
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism*
  • DNA-Binding Proteins
  • Down-Regulation / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Ganglia, Invertebrate / cytology
  • Ganglia, Invertebrate / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Genes, Homeobox / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Abd-B proteins, Drosophila
  • Cyclin E
  • DNA-Binding Proteins
  • Drosophila Proteins
  • GCM protein, Drosophila
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • pros protein, Drosophila
  • abd-A protein, Drosophila