title: Evx1 and Evx2 specify excitatory neurotransmitter fates and suppress inhibitory fates through a Pax2-independent mechanism.
abstract: BACKGROUND
  For neurons to function correctly in neuronal circuitry they must utilize appropriate neurotransmitters. However, even though neurotransmitter specificity is one of the most important and defining properties of a neuron we still do not fully understand how neurotransmitter fates are specified during development. Most neuronal properties are determined by the transcription factors that neurons express as they start to differentiate. While we know a few transcription factors that specify the neurotransmitter fates of particular neurons, there are still many spinal neurons for which the transcription factors specifying this critical phenotype are unknown. Strikingly, all of the transcription factors that have been identified so far as specifying inhibitory fates in the spinal cord act through Pax2. Even Tlx1 and Tlx3, which specify the excitatory fates of dI3 and dI5 spinal neurons work at least in part by down-regulating Pax2.
  
  
  METHODS
  In this paper we use single and double mutant zebrafish embryos to identify the spinal cord functions of Evx1 and Evx2.
  
  
  RESULTS
  We demonstrate that Evx1 and Evx2 are expressed by spinal cord V0v cells and we show that these cells develop into excitatory (glutamatergic) Commissural Ascending (CoSA) interneurons. In the absence of both Evx1 and Evx2, V0v cells still form and develop a CoSA morphology. However, they lose their excitatory fate and instead express markers of a glycinergic fate. Interestingly, they do not express Pax2, suggesting that they are acquiring their inhibitory fate through a novel Pax2-independent mechanism.
  
  
  CONCLUSIONS
  Evx1 and Evx2 are required, partially redundantly, for spinal cord V0v cells to become excitatory (glutamatergic) interneurons. These results significantly increase our understanding of the mechanisms of neuronal specification and the genetic networks involved in these processes.
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.
authors.forename: José L
authors.initials: JL
authors.lastname: Juárez-Morales
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Claus J
authors.initials: CJ
authors.lastname: Schulte
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Pezoa
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Vallejo
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.|Department of Neuroscience and Physiology, SUNY Upstate Medical University, 505 Irving Avenue, Syracuse, NY, 13210, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Hilinski
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: England
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: de Jager
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA. kelewi02@syr.edu.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D059330:GABAergic Neurons / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C484089:Evx2 protein, zebrafish; D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; D029961:Zebrafish Proteins; C425331:evx1 protein, zebrafish; C497320:pax2a protein, zebrafish; D018698:Glutamic Acid; D005998:Glycine