Laminar fate and phenotype specification of cerebellar GABAergic interneurons.

In most CNS regions, the variety of inhibitory interneurons originates from separate pools of progenitors residing in discrete germinal
domains, where they become committed to specific phenotypes and positions during their last mitosis. We show here that GABAergic
interneurons of the rodent cerebellum are generated through a different mechanism. Progenitors for these interneurons delaminate from
the ventricular neuroepithelium of the embryonic cerebellar primordium and continue to proliferate in the prospective white matter
during late embryonic and postnatal development. Young postmitotic interneurons do not migrate immediately to their final destination,
but remain in the prospective white matter for several days. The different interneuron categories are produced according to a
continuous inside-out positional sequence, and cell identity and laminar placement in the cerebellar cortex are temporally related to birth
date. However, terminal commitment does not occur while precursors are still proliferating, and postmitotic cells heterochronically
transplanted to developing cerebella consistently adopt host-specific phenotypes and positions. However, solid grafts of prospective
white matter implanted into the adult cerebellum, when interneuron genesis has ceased, produce interneuron types characteristic of the
donor age. Therefore, specification of cerebellar GABAergic interneurons occurs through a hitherto unknown process, in which postmitotic
neurons maintain broad developmental potentialities and their phenotypic choices are dictated by instructive cues provided by the
microenvironment of the prospective white matter. Whereas in most CNS regions the repertoire of inhibitory interneurons is produced
by recruiting precursors from different origins, in the cerebellum it is achieved by creating phenotypic diversity from a single source.