Formation and specification of a Drosophila dopaminergic precursor cell

Development. 2012 Sep;139(18):3316-25. doi: 10.1242/dev.079525. Epub 2012 Aug 8.

Abstract

Dopaminergic neurons play important roles in animal behavior, including motivation, reward and locomotion. The Drosophila dopaminergic H-cell interneuron is an attractive system for studying the genetics of neural development because analysis is focused on a single neuronal cell type. Here we provide a mechanistic understanding of how MP3, the precursor to the H-cell, forms and acquires its identity. We show that the gooseberry/gooseberry-neuro (gsb/gsb-n) transcription factor genes act to specify MP3 cell fate. It is proposed that single-minded commits neuroectodermal cells to a midline fate, followed by a series of signaling events that result in the formation of a single gsb(+)/gsb-n(+) MP3 cell per segment. The wingless signaling pathway establishes a midline anterior domain by activating expression of the forkhead transcription factors sloppy paired 1 and sloppy paired 2. This is followed by hedgehog signaling that activates gsb/gsb-n expression in a subgroup of anterior cells. Finally, Notch signaling results in the selection of a single MP3, with the remaining cells becoming midline glia. In MP3, gsb/gsb-n direct H-cell development, in large part by activating expression of the lethal of scute and tailup H-cell regulatory genes. Thus, a series of signaling and transcriptional events result in the specification of a unique dopaminergic precursor cell. Additional genetic experiments indicate that the molecular mechanisms that govern MP3/H-cell development might also direct the development of non-midline dopaminergic neurons.

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
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / metabolism*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Wnt1 Protein
  • gsb protein, Drosophila
  • gsb-n protein, Drosophila
  • sim protein, Drosophila
  • wg protein, Drosophila
  • hh protein, Drosophila