title: Transcriptomes of post-mitotic neurons identify the usage of alternative pathways during adult and embryonic neuronal differentiation.
abstract: BACKGROUND
  Understanding the mechanisms by which neurons are generated and specified, and how they integrate into functional circuits is key to being able to treat disorders of the nervous system and acute brain trauma. Much of what we know about neuronal differentiation has been studied in developing embryos, but differentiation steps may be very different during adult neurogenesis. For this reason, we compared the transcriptomes of newly differentiated neurons in zebrafish embryos and adults.
  
  
  RESULTS
  Using a 4tU RNA labeling method, we isolated and sequenced mRNA specifically from cells of one day old embryos and adults expressing the transgene HA-uprt-mcherry under control of the neuronal marker elavl3. By categorizing transcript products into different protein classes, we identified similarities and differences of gene usage between adult and embryonic neuronal differentiation. We found that neurons in the adult brain and in the nervous system of one day old embryos commonly use transcription factors - some of them identical - during the differentiation process. When we directly compared adult differentiating neurons to embryonic differentiating neurons, however, we found that during adult neuronal differentiation, the expression of neuropeptides and neurotransmitter pathway genes is more common, whereas classical developmental signaling through secreted molecules like Hedgehog or Wnt are less enriched, as compared to embryonic stages.
  
  
  CONCLUSIONS
  We conclude that both adult and embryonic differentiating neurons show enriched use of transcription factors compared to surrounding cells. However, adult and embryonic developing neurons use alternative pathways to differentiate. Our study provides evidence that adult neuronal differentiation is distinct from the better characterized embryonic neuronal differentiation process. This important insight and the lists of enriched genes we have identified will now help pave the way to a better understanding of the mechanisms of embryonic and adult neuronal differentiation and how to manipulate these processes.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. tallafuss@uoneuro.uoregon.edu.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tallafuss
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. mwk@uoregon.edu.
authors.forename: Meghan
authors.initials: M
authors.lastname: Kelly
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, OR, USA. esgay@uoneuro.uoregon.edu.
authors.forename: Leslie
authors.initials: L
authors.lastname: Gay
authors.affiliation: Current address: Vollum Institute, Oregon Health and Science University, Portland, OR, USA. gibsoda@ohsu.edu.
authors.forename: Dan
authors.initials: D
authors.lastname: Gibson
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. pbatzel@uoregon.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Batzel
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, OR, USA. karfilis@uoregon.edu.
authors.forename: Kate V
authors.initials: KV
authors.lastname: Karfilis
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. eisen@uoneuro.uoregon.edu.
authors.forename: Judith
authors.initials: J
authors.lastname: Eisen
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, OR, USA. kryn@uoregon.edu.
authors.forename: Kryn
authors.initials: K
authors.lastname: Stankunas
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. jpostle@uoneuro.uoregon.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA. pwash@uoneuro.uoregon.edu.
authors.forename: Philip
authors.initials: P
authors.lastname: Washbourne
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D009479:Neuropeptides; D014157:Transcription Factors