Embryonic Purkinje Cells Grafted on the Surface of the Cerebellar Cortex Integrate in the Adult Unlesioned Cerebellum

Rossi, Ferdinando; Borsello, Tiziana; Strata, Piergiorgio

doi:10.1111/j.1460-9568.1992.tb00908.x

Cited by 30 publications

(10 citation statements)

References 23 publications

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“…To identify donor cells derived from either sources, postnatal tissues were isolated from transgenic mice expressing the LacZ reporter gene in different neuron populations. In such mixed grafts, the embryonic donor tissue developed typical minicerebellar structures (Sotelo and Alvarado-Mallart, 1991; Rossi et al, 1992), while postnatal cells were incorporated as individual elements within this framework. The latter cells exclusively differentiated into ML interneurons and granule cells (the P4 tissue also contained the EGL), indicating that they were strictly committed toward late-generated identities and not responsive to neurogenic cues provided by the embryonic milieu (Jankovski et al, 1996).…”

Section: Spatio-temporal Evolution Of the Developmental Potential Of mentioning

confidence: 99%

The Genesis of Cerebellar GABAergic Neurons: Fate Potential and Specification Mechanisms

2012

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All cerebellar neurons derive from progenitors that proliferate in two germinal neuroepithelia: the ventricular zone (VZ) generates GABAergic neurons, whereas the rhombic lip is the origin of glutamatergic types. Among VZ-derivatives, GABAergic projection neurons, and interneurons are generated according to distinct strategies. Projection neurons (Purkinje cells and nucleo-olivary neurons) are produced at the onset of cerebellar neurogenesis by discrete progenitor pools located in distinct VZ microdomains. These cells are specified within the VZ and acquire mature phenotypes according to cell-autonomous developmental programs. On the other hand, the different categories of inhibitory interneurons derive from a single population of Pax-2-positive precursors that delaminate into the prospective white matter (PWM), where they continue to divide up to postnatal development. Heterotopic/heterochronic transplantation experiments indicate that interneuron progenitors maintain full developmental potentialities up to the end of cerebellar development and acquire mature phenotypes under the influence of environmental cues present in the PWM. Furthermore, the final fate choice occurs in postmitotic cells, rather than dividing progenitors. Extracerebellar cells grafted to the prospective cerebellar white matter are not responsive to local neurogenic cues and fail to adopt clear cerebellar identities. Conversely, cerebellar cells grafted to extracerebellar regions retain typical phenotypes of cerebellar GABAergic interneurons, but acquire type-specific traits under the influence of local cues. These findings indicate that interneuron progenitors are multipotent and sensitive to spatio-temporally patterned environmental signals that regulate the genesis of different categories of interneurons, in precise quantities and at defined times and places.

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Section: Spatio-temporal Evolution Of the Developmental Potential Of mentioning

confidence: 99%

The Genesis of Cerebellar GABAergic Neurons: Fate Potential and Specification Mechanisms

2012

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“…Solid grafts of PWM were prepared by carefully dissecting small tissue blocks from the periventricular region of the donor cerebellum (Leto et al, 2006). One or two of these blocks were pressure injected in each recipient cerebellum via a glass capillary, according to previously established procedures (Rossi et al, 1992). Single-cell suspensions were obtained by mechanical dissociation of embryonic cerebellar primordia or of tissue blocks from postnatal cerebella.…”

Section: Transplantation Experimentsmentioning

confidence: 99%

Laminar Fate and Phenotype Specification of Cerebellar GABAergic Interneurons

et al. 2009

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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.

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“…A number of previous studies (Sotelo and Alvarado-Mallart, 1987;Gardette et al, 1990;Sotelo et al, 1990;Rossi et al, 1992Rossi et al, , 1994 showed that grafted immature PCs integrate into the mature host cerebellum. These grafted PCs receive synaptic inputs from PFs, inhibitory interneurons, and CFs Sotelo et al, 1990;Tempia et al, 1996), and they interact with the host Bergman glia.…”

Section: Pc Maturation Regulates the Number Of Reinnervating Cfs: Dirmentioning

confidence: 99%

Reinnervation of Late Postnatal Purkinje Cells by Climbing Fibers: Neosynaptogenesis without Transient Multi-Innervation

Letellier¹,

Bailly²,

Demais³

et al. 2007

J. Neurosci.

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Synaptic partner selection and refinement of projections are important in the development of precise and functional neuronal connections. We investigated the formation of new synaptic connections in a relatively mature system to test whether developmental events can be recapitulated at later stages (i.e., after the mature synaptic organization has been established), using a model of postlesional reinnervation in the olivo-cerebellar pathway.During the development of this pathway, synaptic connections between climbing fibers (CFs) and Purkinje cells (PCs) are diffuse and redundant before synapse elimination refines the pattern. The regression of CFs during the first 2 postnatal weeks in the rat leads to mono-innervation of each PC. After unilateral transection of the rat olivo-cerebellar pathway and intracerebellar injection of BDNF 24 h after lesion, axons from the remaining inferior olive can sprout into the deafferented hemicerebellum and establish new contacts with denervated PCs at later developmental stages. We found that these contacts are first established on somatic thorns before the CFs translocate to the PC dendrites, recapitulating the morphological steps of normal CF-PC synaptogenesis, but on a relatively mature PC.However, electrophysiology of PC reinnervation by transcommissural CFs in these animals showed that each PC is reinnervated by only one CF. This mono-innervation contrasts with the reinnervation of grafted immature PCs in the same cerebellum. Our results provide evidence that relatively mature PCs do not receive several olivary afferents during late reinnervation, suggesting a critical role of the target cell state in the control of CF-PC synaptogenesis. Thus, synapse exuberance and subsequent elimination are not a prerequisite to reach a mature relationship between synaptic partners.

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Embryonic Purkinje Cells Grafted on the Surface of the Cerebellar Cortex Integrate in the Adult Unlesioned Cerebellum

Cited by 30 publications

References 23 publications

The Genesis of Cerebellar GABAergic Neurons: Fate Potential and Specification Mechanisms

The Genesis of Cerebellar GABAergic Neurons: Fate Potential and Specification Mechanisms

Laminar Fate and Phenotype Specification of Cerebellar GABAergic Interneurons

Reinnervation of Late Postnatal Purkinje Cells by Climbing Fibers: Neosynaptogenesis without Transient Multi-Innervation

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