Brain Structure and Function

, Volume 222, Issue 6, pp 2787–2805 | Cite as

Mtss1 promotes maturation and maintenance of cerebellar neurons via splice variant-specific effects

  • Thorsten Sistig
  • Fanziska Lang
  • Sebastian Wrobel
  • Stephan L. Baader
  • Karl Schilling
  • Britta EibergerEmail author
Original Article


Efficient coupling of the actin cytoskeleton to the cell membrane is crucial for histogenesis and maintenance of the nervous system. At this critical interface, BAR (Bin–Amphiphysin–Rvs) proteins regulate membrane bending, shown to be instrumental for mobility and morphogenesis of individual cells. Yet, the systemic significance of these proteins remains largely unexplored. Here, we probe the role of a prominent member of this protein family, the inverse-BAR protein Mtss1, for the development and function of a paradigmatic neuronal circuit, the cerebellar cortex. Mtss1-null mice show granule cell ectopias, dysmorphic Purkinje cells, malformed axons, and a protracted neurodegeneration entailing age-dependent motor deficits. In postmitotic granule cells, which transiently express Mtss1 while they migrate and form neurites, Mtss1 impinges on directional persistence and neuritogenesis. The latter effect can be specifically attributed to its exon 12a splice variant. Targeted re-expression of Mtss1 in Mtss1-null animals indicated that these pathologies were largely due to cell type-specific and intrinsic effects. Together, our results provide a mechanistic perspective on Mtss1 function for brain development and degeneration and relate it to structural features of this protein.


Actin cytoskeleton Cell migration Neuritogenesis Neurodegeneration 



We gratefully acknowledge the generous gift of Mtss1-deficient animals by Dr. Rong Li; of Atoh1-cre animals by Dr. Ulrich Schüller and Pcp2-cre mice by Dr. Michael Meyer. We are greatly indebted to Andrea Christ and Helma Langmann for excellent technical assistance, Daniela Krauss and Narziss Haias for invaluable help with animal husbandry; Alexander Glassmann and Kirsten Knapp for providing plasmids containing Mtss1-cDNA, and to Benjamin Odermatt for many constructive discussions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

429_2017_1372_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 KB)
429_2017_1372_MOESM2_ESM.jpg (1.1 mb)
Supplementary material 2 (JPG 1122 KB)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Thorsten Sistig
    • 1
  • Fanziska Lang
    • 1
  • Sebastian Wrobel
    • 1
  • Stephan L. Baader
    • 1
  • Karl Schilling
    • 1
  • Britta Eiberger
    • 1
    Email author
  1. 1.Anatomisches Institut, Anatomie and ZellbiologieUniversity of BonnBonnGermany

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