Leto Ketty, Bartolini Alice, Yanagawa Yukio, Obata Kunihiko, Magrassi Lorenzo, Schilling Karl, Rossi Ferdinando
Department of Neuroscience and Rita Levi-Montalcini Center for Brain Repair, Neuroscience Institute of Turin, University of Turin, I-10125 Turin, Italy.
J Neurosci. 2009 May 27;29(21):7079-91. doi: 10.1523/JNEUROSCI.0957-09.2009.
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.
在大多数中枢神经系统区域，抑制性中间神经元的多样性源自位于离散生发区的不同祖细胞池，在那里它们在最后一次有丝分裂期间确定特定的表型和位置。我们在此表明，啮齿动物小脑的γ-氨基丁酸能中间神经元是通过不同机制产生的。这些中间神经元的祖细胞从胚胎小脑原基的室管膜神经上皮脱层，并在胚胎后期和出生后发育期间在前瞻性白质中继续增殖。年轻的有丝分裂后中间神经元不会立即迁移到它们的最终目的地，而是在前瞻性白质中停留数天。不同类型的中间神经元是按照从内向外的连续位置序列产生的，并且小脑皮质中的细胞身份和层状位置在时间上与出生日期相关。然而，在前体仍在增殖时不会发生终末确定，并且异时移植到发育中小脑的有丝分裂后细胞始终采用宿主特异性的表型和位置。然而，当中间神经元发生停止时，植入成年小脑中的前瞻性白质实体移植物会产生供体年龄特征性的中间神经元类型。因此，小脑γ-氨基丁酸能中间神经元的特化是通过一个迄今未知的过程发生的，在这个过程中，有丝分裂后神经元保持广泛的发育潜能，它们的表型选择由前瞻性白质微环境提供的指导性线索决定。在大多数中枢神经系统区域，抑制性中间神经元的种类是通过从不同来源招募前体产生的，而在小脑中，它是通过从单一来源创造表型多样性来实现的。
