The Cerebellum

, Volume 16, Issue 1, pp 122–131 | Cite as

Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum

  • Annika K. Wefers
  • Sven Lindner
  • Johannes H. Schulte
  • Ulrich Schüller
Original Paper
First Online:

Abstract

LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors. Sections of the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice appeared normal, but we found a pronounced vermal hypersublobulation at p15 and p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15 than in controls, contained more proliferating cells, and persisted up to p21. Consistently, some Pax6- and NeuN-positive cells were present in the EGL of Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive granule neuron precursors in the molecular layer (ML) as compared to control. Finally, we found some residual Pax2-positive precursors of inhibitory interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already disappeared in controls. We conclude that while overexpression of LIN28B in Nestin-positive cells does not lead to tumor formation, it results in a protracted development of granule cells and inhibitory interneurons and leads to a hypersublobulation of the cerebellar vermis.

Keywords

Cerebellum LIN28B Nestin Hypersublobulation Development Tumor 
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Notes

Acknowledgments

We are indebted to Michael Schmidt, Silvia Occhionero, and Marie-Christin Burmester for the excellent technical support. This work was supported by grants from the German Cancer Aid and the Wilhelm-Sander Stiftung.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Center for NeuropathologyLudwig-Maximilians-UniversityMunichGermany
  2. 2.Department of Neuropathology, Institute of PathologyRuprecht-Karls-University HeidelbergHeidelbergGermany
  3. 3.Department of Pediatric Oncology and HematologyUniversity Hospital EssenEssenGermany
  4. 4.Pediatric Oncology and HematologyCharité University MedicineBerlinGermany

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