Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate

Development. 2011 Jun;138(11):2171-83. doi: 10.1242/dev.056507.

Abstract

Dopaminergic neurons play important behavioral roles in locomotion, reward and aggression. The Drosophila H-cell is a dopaminergic neuron that resides at the midline of the ventral nerve cord. Both the H-cell and the glutamatergic H-cell sib are the asymmetric progeny of the MP3 midline precursor cell. H-cell sib cell fate is dependent on Notch signaling, whereas H-cell fate is Notch independent. Genetic analysis of genes that could potentially regulate H-cell fate revealed that the lethal of scute [l(1)sc], tailup and SoxNeuro transcription factor genes act together to control H-cell gene expression. The l(1)sc bHLH gene is required for all H-cell-specific gene transcription, whereas tailup acts in parallel to l(1)sc and controls genes involved in dopamine metabolism. SoxNeuro functions downstream of l(1)sc and controls expression of a peptide neurotransmitter receptor gene. The role of l(1)sc may be more widespread, as a l(1)sc mutant shows reductions in gene expression in non-midline dopaminergic neurons. In addition, l(1)sc mutant embryos possess defects in the formation of MP4-6 midline precursor and the median neuroblast stem cell, revealing a proneural role for l(1)sc in midline cells. The Notch-dependent progeny of MP4-6 are the mVUM motoneurons, and these cells also require l(1)sc for mVUM-specific gene expression. Thus, l(1)sc plays an important regulatory role in both neurogenesis and specifying dopaminergic neuron and motoneuron identities.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Central Nervous System / embryology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dopamine / metabolism
  • Drosophila / cytology
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Motor Neurons / cytology
  • Motor Neurons / physiology*
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / physiology*
  • Receptors, Neurotransmitter / biosynthesis
  • Receptors, Neurotransmitter / genetics
  • Receptors, Notch / metabolism
  • SOX Transcription Factors / genetics
  • SOX Transcription Factors / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Receptors, Neurotransmitter
  • Receptors, Notch
  • SOX Transcription Factors
  • SoxN protein, Drosophila
  • Transcription Factors
  • ac protein, Drosophila
  • l(1)sc protein, Drosophila
  • sc protein, Drosophila
  • tup protein, Drosophila
  • Dopamine