title: Pax3 isoforms in sensory neurogenesis: expression and function in the ophthalmic trigeminal placode.
abstract: BACKGROUND
  In the trigeminal placode, Pax3 is classified as necessary but not sufficient for sensory neuron differentiation. One hypothesis is that different Pax3 isoforms regulate cellular differentiation uniquely. Pax3 is known to sometimes activate and sometimes repress gene transcription, and its activity can be dependent on the isoforms present. Pax3 isoforms had not previously been characterized in chick sensory neurogenesis.
  
  
  RESULTS
  Reverse transcriptase-polymerase chain reaction (PCR) analysis revealed three well-expressed Pax3 splice variants: full-length (flPax3), Pax3V1, and Pax3V2. Each was characterized for its effect on neurogenesis by misexpression in placodal ectoderm. The differences observed were more apparent under conditions of enhanced neurogenesis (by means of Notch inhibition), where flPax3 and Pax3V1 caused failed differentiation, while Pax3V2 misexpression resembled the neuronal differentiation seen in controls. Quantitative PCR analysis revealed a progressive increase in Pax3 expression, but no significant change in relative isoform expression. Of interest, Notch inhibition led to a significant increase in Pax3 expression.
  
  
  CONCLUSIONS
  We can conclude that: (1) flPax3 and Pax3V1 inhibit neuronal differentiation; (2) Pax3V2 is permissive for neuronal differentiation; (3) while absolute levels change over time, relative splice form expression levels are largely maintained in the trigeminal placode domain; and (4) Pax3 expression generally increases in response to Notch inhibition.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Adams
authors.forename: Sterling N
authors.initials: SN
authors.lastname: Sudweeks
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stark
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D046149:Embryo Culture Techniques; D018507:Gene Expression Regulation, Developmental; D055495:Neurogenesis / Q000235:genetics*; D009882:Ophthalmic Nerve / Q000196:embryology* / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology; D012668:Trigeminal Ganglion / Q000196:embryology* / Q000378:metabolism*
chemical_list: D051761:Paired Box Transcription Factors; D020033:Protein Isoforms
keywords: Notch signaling; Pax3; alternative splicing; isoforms; splice variants; transactivation domain; trigeminal placode