Different types of cerebellar GABAergic interneurons originate from a common pool of multipotent progenitor cells.
Different cerebellar phenotypes are generated according to a precise spatiotemporal schedule, in which projection neurons precede local interneurons. Glutamatergic neurons develop from the rhombic lip, whereas GABAergic neurons originate from the ventricular neuroepithelium. Progenitors in these germinal layers are committed toward specific phenotypes already at early ontogenetic stages. GABAergic interneurons are thought to derive from a subset of ventricular zone cells, which migrate in the white matter and proliferate up to postnatal life. During this period, different interneuron categories are produced according to an inside-out sequence, from the deep nuclei to the molecular layer (we show here that nuclear interneurons are also born during late embryonic and early postnatal days, after glutamatergic and GABAergic projection neurons). To ask whether distinct interneuron phenotypes share common precursors or derive from multiple fate-restricted progenitors, we examined the behavior of embryonic and postnatal rat cerebellar cells heterotopically/heterochronically transplanted to syngenic hosts. In all conditions, donor cells achieved a high degree of integration in the cerebellar cortex and deep nuclei and acquired GABAergic interneuron phenotypes appropriate for the host age and engraftment site. Therefore, contrary to other cerebellar types, which derive from dedicated precursors, GABAergic interneurons are produced by a common pool of progenitors, which maintain their full developmental potentialities up to late ontogenetic stages and adopt mature identities in response to local instructive cues. In this way, the numbers and types of inhibitory interneurons can be set by spatiotemporally patterned signals to match the functional requirements of developing cerebellar circuits.
Leto
Ketty
K
Department of Neuroscience and Rita Levi Montalcini Centre for Brain Repair, University of Turin, 10125 Turin, Italy.
Carletti
Barbara
B
Williams
Ian Martin
IM
Magrassi
Lorenzo
L
Rossi
Ferdinando
F
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods; D002531:Cerebellum / Q000166:cytology*; D003911:Dextrans / Q000378:metabolism; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D003911:Dextrans; C067661:Fluoro-Ruby; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; D012235:Rhodamines; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D001973:Bromodeoxyuridine