title: Neuromancer1 and Neuromancer2 regulate cell fate specification in the developing embryonic CNS of Drosophila melanogaster.
abstract: T-box genes encode a large family of transcription factors that regulate many developmental processes in vertebrates and invertebrates. In addition to their roles in regulating embryonic heart and epidermal development in Drosophila, we provide evidence that the T-box transcription factors neuromancer1 (nmr1) and neuromancer2 (nmr2) play key roles in embryonic CNS development. We verify that nmr1 and nmr2 function in a partially redundant manner to regulate neuronal cell fate by inhibiting even-skipped (eve) expression in specific cells in the CNS. Consistent with their redundant function, nmr1 and nmr2 exhibit overlapping yet distinct protein expression profiles within the CNS. Of note, nmr2 transcript and protein are expressed in identical patterns of segment polarity stripes, defined sets of neuroblasts, many ganglion mother cells and discrete populations of neurons. However, while we observe nmr1 transcripts in segment polarity stripes and specific neural precursors in early stages of CNS development, we first detect Nmr1 protein in later stages of CNS development where it is restricted to discrete subsets of Nmr2-positive neurons. Expression studies identify nearly all Nmr1/2 co-expressing neurons as interneurons, while a single Eve-positive U/CQ motor neuron weakly co-expresses Nmr2. Lineage studies map a subset of Nmr1/2-positive neurons to neuroblast lineages 2-2, 6-1, and 6-2 while genetic studies reveal that nmr2 collaborates with nkx6 to regulate eve expression in the CNS. Thus, nmr1 and nmr2 appear to act together as members of the combinatorial code of transcription factors that govern neuronal subtype identity in the CNS.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. sandra.leal@usm.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Leal
authors.forename: L
authors.initials: L
authors.lastname: Qian
authors.forename: H
authors.initials: H
authors.lastname: Lacin
authors.forename: R
authors.initials: R
authors.lastname: Bodmer
authors.forename: J B
authors.initials: JB
authors.lastname: Skeath
mesh_terms: D000818:Animals; D019521:Body Patterning; D019070:Cell Lineage; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000201:enzymology; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C495572:H15 protein, Drosophila; C471705:HGTX protein, Drosophila; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C052837:eve protein, Drosophila; C495571:mid protein, Drosophila; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase