title: Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate.
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.
authors.affiliation: Curriculum in Neurobiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Stagg
authors.forename: Amaris R
authors.initials: AR
authors.lastname: Guardiola
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Crews
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism; D055747:SOX Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D004298:Dopamine; D029721:Drosophila Proteins; D017981:Receptors, Neurotransmitter; D051880:Receptors, Notch; D055747:SOX Transcription Factors; D014157:Transcription Factors; C412366:SoxN protein, Drosophila; C089199:ac protein, Drosophila; C089200:l(1)sc protein, Drosophila; C089197:sc protein, Drosophila; C494337:tup protein, Drosophila