title: Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics.
abstract: BACKGROUND
  Precise matching between motoneuron subtypes and the muscles they innervate is a prerequisite for normal behavior. Motoneuron subtype identity is specified by the combination of transcription factors expressed by the cell during its differentiation. Here we investigate the roles of Mnx family transcription factors in specifying the subtypes of individually identified zebrafish primary motoneurons.
  
  
  RESULTS
  Zebrafish has three Mnx family members. We show that each of them has a distinct and temporally dynamic expression pattern in each primary motoneuron subtype. We also show that two Mnx family members are expressed in identified VeLD interneurons derived from the same progenitor domain that generates primary motoneurons. Surprisingly, we found that Mnx proteins appear unnecessary for differentiation of VeLD interneurons or the CaP motoneuron subtype. Mnx proteins are, however, required for differentiation of the MiP motoneuron subtype. We previously showed that MiPs require two temporally-distinct phases of Islet1 expression for normal development. Here we show that in the absence of Mnx proteins, the later phase of Islet1 expression is initiated but not sustained, and MiPs become hybrids that co-express morphological and molecular features of motoneurons and V2a interneurons. Unexpectedly, these hybrid MiPs often extend CaP-like axons, and some MiPs appear to be entirely transformed to a CaP morphology.
  
  
  CONCLUSIONS
  Our results suggest that Mnx proteins promote MiP subtype identity by suppressing both interneuron development and CaP axon pathfinding. This is, to our knowledge, the first report of transcription factors that act to distinguish CaP and MiP subtype identities. Our results also suggest that MiP motoneurons are more similar to V2 interneurons than are CaP motoneurons.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA.
authors.forename: Steve D
authors.initials: SD
authors.lastname: Seredick
authors.forename: Liesl
authors.initials: L
authors.lastname: Van Ryswyk
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Hutchinson
authors.forename: Judith S
authors.initials: JS
authors.lastname: Eisen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D009046:Motor Neurons / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060850:LIM-Homeodomain Proteins; C531385:Mnx1 protein, zebrafish; D060172:Morpholinos; D014157:Transcription Factors; D029961:Zebrafish Proteins; C063843:insulin gene enhancer binding protein Isl-1; D049452:Green Fluorescent Proteins