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Exogenous Sonic Hedgehog Modulates the Pool of GABAergic Interneurons During Cerebellar Development

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Abstract

All cerebellar GABAergic interneurons were derived from a common pool of precursor cells residing in the embryonic ventricular zone (VZ) and migrating in the prospective white matter (PWM) after birth, where both intrinsic and extrinsic factors contribute to regulate their amplification. Among the environmental factors, we focused on Sonic hedgehog (Shh), a morphogen well known to regulate neural progenitor cell proliferation. We asked if and how exogenous Shh treatment affects the lineage of cerebellar GABAergic interneurons. To address these issues, exogenous Shh was administered to embryonic and postnatal organotypic slices. We found that Shh is able to expand the pool of interneuron progenitors residing in the embryonic epithelium and in the postnatal PWM. In particular, Shh signalling pathway was highly mitogenic at early developmental stages of interneuron production, whereas its effect decreased after the first postnatal week. Gene expression analysis of sorted cells and in situ hybridization further showed that immature interneurons express both the Shh receptor patched and the Shh target gene Gli1. Thus, within the interneuron lineage, Shh might exert regulatory functions also in postmitotic cells. On the whole, our data enlighten the role of Shh during cerebellar maturation and further broaden our knowledge on the amplification mechanisms of the interneuron progenitor pool.

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Acknowledgements

We would like to dedicate this work in memoriam of Prof F. Rossi, for continuous support and encouragement. We thank Dr. Paola Bernabei for help in FAC Sorter analysis. This work was supported by grants from Ministero dell’Università e della Ricerca (PRIN 2009 program no. TBCZJB to F.R. and Ricerca Fondo per l’Incentivazione della Ricerca di Base research grant RBFR10A01S to K.L.).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10026, Turin, Italy

    A. De Luca, E. Parmigiani, G. Tosatto, A. Buffo, K. Leto & F. Rossi

  2. Neuroscience Institute Cavalieri-Ottolenghi, University of Turin, Regione Gonzole 10, 10043, Orbassano, Turin, Italy

    A. De Luca, E. Parmigiani, G. Tosatto, S. Martire, A. Buffo, K. Leto & F. Rossi

  3. Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan

    M. Hoshino

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Correspondence to K. Leto.

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De Luca, A., Parmigiani, E., Tosatto, G. et al. Exogenous Sonic Hedgehog Modulates the Pool of GABAergic Interneurons During Cerebellar Development. Cerebellum 14, 72–85 (2015). https://doi.org/10.1007/s12311-014-0596-x

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