Dataset Information

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.

ABSTRACT: BACKGROUND: Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated. RESULTS: We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step. CONCLUSIONS: Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.

SUBMITTER: Miyata T

PROVIDER: S-EPMC2942860 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Publications

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.

Miyata Takaki T Ono Yuichi Y Okamoto Mayumi M Masaoka Makoto M Sakakibara Akira A Kawaguchi Ayano A Hashimoto Mitsuhiro M Ogawa Masaharu M

Neural development 20100901

<h4>Background</h4>Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nas ...[more]

PMID: 20809939

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Project description:Mounting evidence indicates that posterolateral portions of the cerebellum (right Crus I/II) contribute to language processing, but the nature of this role remains unclear. Based on a well-supported theory of cerebellar motor function, which ascribes to the cerebellum a role in short-term prediction through internal modeling, we hypothesize that right cerebellar Crus I/II supports prediction of upcoming sentence content. We tested this hypothesis using event-related fMRI in male and female human subjects by manipulating the predictability of written sentences. Our design controlled for motor planning and execution, as well as for linguistic features and working memory load; it also allowed separation of the prediction interval from the presentation of the final sentence item. In addition, three further fMRI tasks captured semantic, phonological, and orthographic processing to shed light on the nature of the information processed. As hypothesized, activity in right posterolateral cerebellum correlated with the predictability of the upcoming target word. This cerebellar region also responded to prediction error during the outcome of the trial. Further, this region was engaged in phonological, but not semantic or orthographic, processing. This is the first imaging study to demonstrate a right cerebellar contribution in language comprehension independently from motor, cognitive, and linguistic confounds. These results complement our work using other methodologies showing cerebellar engagement in linguistic prediction and suggest that internal modeling of phonological representations aids language production and comprehension.SIGNIFICANCE STATEMENT The cerebellum is traditionally seen as a motor structure that allows for smooth movement by predicting upcoming signals. However, the cerebellum is also consistently implicated in nonmotor functions such as language and working memory. Using fMRI, we identify a cerebellar area that is active when words are predicted and when these predictions are violated. This area is active in a separate task that requires phonological processing, but not in tasks that require semantic or visuospatial processing. Our results support the idea of prediction as a unifying cerebellar function in motor and nonmotor domains. We provide new insights by linking the cerebellar role in prediction to its role in verbal working memory, suggesting that these predictions involve phonological processing.

Dataset Information

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.

Publications

Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.

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