title: Exogenous Sonic hedgehog modulates the pool of GABAergic interneurons during cerebellar development.
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.
authors.affiliation: Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10026, Turin, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: E
authors.initials: E
authors.lastname: Parmigiani
authors.forename: G
authors.initials: G
authors.lastname: Tosatto
authors.forename: S
authors.initials: S
authors.lastname: Martire
authors.forename: M
authors.initials: M
authors.lastname: Hoshino
authors.forename: A
authors.initials: A
authors.lastname: Buffo
authors.forename: K
authors.initials: K
authors.lastname: Leto
authors.forename: F
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000008:administration & dosage / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D000071676:Zinc Finger Protein GLI1
chemical_list: D002491:Central Nervous System Agents; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D000071676:Zinc Finger Protein GLI1