Advertisement

The Cerebellum

, Volume 14, Issue 1, pp 12–14 | Cite as

LGI1 is Involved in the Development of Mouse Brain

  • Li-Da Su
  • Ya-Jun Xie
  • Liang Zhou
  • Ying Shen
  • Ying-Hong Hu
Review

Abstract

Mutations in leucine-rich glioma inactivated 1 (LGI1) are linked to human autosomal dominant lateral temporal lobe epilepsy. It has been shown that LGI1 prevents the inactivation of voltage-gated potassium channels, mediates postnatal maturation of glutamatergic synapses, and regulates excitatory neurotransmission. However, other functions of LGI1 in the central nervous system have not been elucidated. We found that LGI1 is involved in the development of the cerebellum and cortex. The thickness of external granule layer was reduced, and foliation was affected in the cerebellum of LGI1 knockout mice. Double staining with Pax6 and BrdU showed a significant inhibition of proliferation of granule cell precursors of knockout embryos. The differentiation of radial glia cells was also suppressed in knockout mice, as shown by increased radial glial cells and decreased Bergmann glias in the areas of the cerebellum and cortex. Thus, our data demonstrate that LGI1 may be an essential player in the development of the brain.

Keywords

LGI1 Cerebellum GFAP Pax6 BLBP 

Notes

Acknowledgments

We thank Dr. John Cowell (Georgia Health Sciences University, Augusta, AT) for providing the LGI1-KO mice. This work was supported by the National Foundation of Natural Science of China (31100780 and 31200818), the Public Benefit Research Project of Zhejiang Province Department of Science and Technology (2013C33233), Seeds Fund for Interdisciplinary Research at Zhejiang University (JCZZ-2013037), and the Foundation of Zhejiang Educational Committee (Y201121662 and Y20070109).

Conflicts of Interest

There are no conflicts of interest for Li-Da Su, Ya-Jun Xie, Liang Zhou, Ying Shen, and Ying-Hong Hu.

References

  1. 1.
    Kegel L, Aunin E, Meijer D, Bermingham JR. LGI protein in the nervous system. ASN Neuro. 2013;5:167–81.PubMedCrossRefGoogle Scholar
  2. 2.
    Nobile C, Michelucci R, Andreazza S, Pasini E, Tosatto SC, Striano P. LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat. 2009;30:530–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Yu YE, Wen L, Silva J, Li Z, Head K, Sossey-Alaoui K, et al. Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability. Hum Mol Genet. 2010;19:1702–11.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Schulte U, Thumfart JO, Klöcker N, Sailer CA, Bildl W, Biniossek M, et al. The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron. 2006;49:697–706.PubMedCrossRefGoogle Scholar
  5. 5.
    Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M. Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science. 2006;313:1792–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Zhou YD, Lee S, Jin Z, Wright M, Smith SE, Anderson MP. Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat Med. 2009;15:1208–14.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Sagane K, Ishihama Y, Sugimoto H. LGI1 and LGI4 bind to ADAM22, ADAM23 and ADAM11. Inter J Biol Sci. 2008;4:387–96.CrossRefGoogle Scholar
  8. 8.
    Thomas R, Favell K, Morante-Redolat J, Pool M, Kent C, Wright M, et al. LGI1 is a Nogo receptor 1 ligand that antagonizes myelin-based growth inhibition. J Neurosci. 2010;30:6607–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Kusuzawa S, Honda T, Fukata Y, Fukata M, Kanatani S, Tanaka DH, et al. Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein, has a nuclear localization signal and localizes to both the cytoplasm and the nucleus of the caudal ganglionic eminence neurons. Eur J Neurosci. 2012;36:2284–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Xu H, Yang Y, Tang X, Zhao M, Liang F, Xu P, et al. Bergmann glia function in granule cell migration during cerebellum development. Mol Neurobiol. 2010;47:833–44.CrossRefGoogle Scholar
  11. 11.
    Dahmane N, Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 1999;126:3089–3100.Google Scholar
  12. 12.
    Vaillant C, Monard D. SHH pathway and cerebellar development. Cerebellum. 2009;8:291–301.PubMedCrossRefGoogle Scholar
  13. 13.
    Sudarov A, Joyner AL. Cerebellum morphogenesis: the foliation pattern is orchestrated by multi-cellular anchoring centers. Neural Dev. 2007;2:26.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Anthony TE, Mason HA, Gridley T, Fishell G, Heintz N. Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells. Genes Dev. 2005;19:1028–33.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Schmid RS, McGrath B, Berechid BE, Boyles B, Marchionni M, Sestan N, et al. Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A. 2003;100:4251–6.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Neuroscience Care UnitThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouPeople’s Republic of China
  2. 2.Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of HealthZhejiang University School of MedicineHangzhouPeople’s Republic of China

Personalised recommendations