title: Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells.
abstract: BACKGROUND
  Mtss1 encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of Mtss1 in the developing murine cerebellum and human medulloblastoma specimens.
  
  
  RESULTS
  During development, Mtss1 is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of Mtss1, and one also harbors a potential PKA and PKC phosphorylation site.
  
  
  CONCLUSIONS
  Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons.
authors.affiliation: Anatomisches Institut, Anatomie & Zellbiologie, University of Bonn, Bonn, Germany. alexander.glassmann@uni-bonn.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Glassmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Molly
authors.forename: Lachezar
authors.initials: L
authors.lastname: Surchev
authors.forename: Tommy A
authors.initials: TA
authors.lastname: Nazwar
authors.forename: Martin
authors.initials: M
authors.lastname: Holst
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartmann
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Baader
authors.forename: John
authors.initials: J
authors.lastname: Oberdick
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Karl
authors.initials: K
authors.lastname: Schilling
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002528:Cerebellar Neoplasms / Q000473:pathology; D002531:Cerebellum / Q000254:growth & development* / Q000473:pathology; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019154:Protein Splicing / Q000235:genetics; D011689:Purkinje Cells / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins