title: Clustered fine compartmentalization of the mouse embryonic cerebellar cortex and its rearrangement into the postnatal striped configuration.
abstract: Compartmentalization is essential for a brain area to be involved in different functions through topographic afferent and efferent connections that reflect this organization. The adult cerebellar cortex is compartmentalized into longitudinal stripes, in which Purkinje cells (PCs) have compartment-specific molecular expression profiles. How these compartments form during development is generally not understood. To investigate this process, we focused on the late developmental stages of the cerebellar compartmentalization that occur from embryonic day 17.5 (E17.5), when embryonic compartmentalization is evidently observed, to postnatal day 6 (P6), when adult-type compartmentalization begins to be established. The transformation between these compartmentalization patterns was analyzed by mapping expression patterns of several key molecular markers in serial cerebellar sections in the mouse. A complete set of 54 clustered PC subsets, which had different expression profiles of FoxP2, PLCβ4, EphA4, Pcdh10, and a reporter molecule of the 1NM13 transgenic mouse strain, were distinguished in three-dimensional space in the E17.5 cerebellum. Following individual PC subsets during development indicated that these subsets were rearranged from a clustered and multilayered configuration to a flattened, single-layered and striped configuration by means of transverse slide, longitudinal split, or transverse twist spatial transformations during development. The Purkinje cell-free spaces that exist between clusters at E17.5 become granule cell raphes that separate striped compartments at P6. The results indicate that the ∼50 PC clusters of the embryonic cerebellum will ultimately become the longitudinal compartments of the adult cerebellum after undergoing various peri- and postnatal transformations that alter their relative spatial relationships.
authors.affiliation: Department of Systems Neurophysiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8519, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Morita
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
authors.forename: Izumi
authors.initials: I
authors.lastname: Sugihara
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002525:Cerebellar Cortex / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism; D000091363:Protocadherins; D011689:Purkinje Cells / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; C117277:Pcdh10 protein, mouse; D000091363:Protocadherins; D012097:Repressor Proteins; D036122:Receptor, EphA4; D054799:Phospholipase C beta; C518043:Plcb4 protein, mouse