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

• Published in: Cerebellum (London, England) Vol. 14; no. 2; pp. 72 - 85
• Main Authors: De Luca, A., Parmigiani, E., Tosatto, G., Martire, S., Hoshino, M., Buffo, A., Leto, K., Rossi, F.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2015; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Proliferation - physiology; Central Nervous System Agents - administration & dosage; Central Nervous System Agents - metabolism; Cerebellum - drug effects; Cerebellum - growth & development; Cerebellum - physiology; GABAergic Neurons - drug effects; GABAergic Neurons - physiology; Gene Expression; Hedgehog Proteins - administration & dosage; Hedgehog Proteins - metabolism; Interneurons - drug effects; Interneurons - physiology; Kruppel-Like Transcription Factors - metabolism; Mice, Inbred C57BL; Mice, Transgenic; Neural Stem Cells - drug effects; Neural Stem Cells - physiology; Neurobiology; Neurology; Neurosciences; Original Paper; PAX2 Transcription Factor - metabolism; Signal Transduction; Tissue Culture Techniques; Zinc Finger Protein GLI1; Cell proliferation; Gli1 expression; Organotypic slices; Pax-2-positive interneurons
• ISSN: 1473-4222; 1473-4230
• DOI: 10.1007/s12311-014-0596-x

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.