Transverse zones in the vermis of the mouse cerebellum

The mouse cerebellar cortex is subdivided by an elaborate array of parasagittal and transverse boundaries. The relationship between these two orthogonal patterns of compartmentation is understood poorly. We have combined the use of adult and perinatal molecular markers of compartmentation—zebrin II, calbindin, and an L7/pcp-2-lacZ transgene—to resolve some of these issues. Our results indicate that the adult cerebellar vermis is divided along the rostrocaudal axis by three transverse boundaries: through the rostral face of lobule VI, in the caudal half of lobule VII, and across the posterolateral fissure between lobules IX and X. These three boundaries subdivide the vermis into four transverse zones: the anterior zone (lobules I–V), the central zone (lobules VI–VII), the posterior zone (lobules VIII–IX), and the nodular zone (lobule X). The same zones and boundaries also can be identified in the newborn cerebellum. The parasagittal organization is different in each zone: a unique combination of Purkinje cell phenotypes is found in each transverse zone both in the neonate and the adult, and different zones have distinct developmental time tables. Furthermore, the parasagittal bands of Purkinje cells revealed in the adult cerebellar cortex by using antizebrin II immunocytochemistry are discontinuous across the transverse boundaries. These data suggest that the transverse zones of the vermis form first during development and that parasagittal compartmentation develops independently in each transverse zone. J. Comp. Neurol. 412:95–111, 1999. © 1999 Wiley-Liss, Inc.     

Antigenic compartmentation of the cerebellar cortex in the chicken (Gallus domesticus)

The chick is a well‐understood developmental model of cerebellar pattern formation,but we know much less about the patterning of the adult chicken cerebellum. Therefore an expression study of two Purkinje cell stripe antigens—zebrin II/aldolase C and phospholipase Cβ4 (PLCβ4)—has been carried out in the adult chicken (Gallus domesticus). The mammalian cerebellar cortex is built around transverse expression domains (“transverse zones”), each of which is further subdivided into parasagittally oriented stripes. The results from the adult chicken reveal a similar pattern. Five distinct transverse domains were identified. In the anterior lobe a uniformly zebrin II‐immunopositive/PLCβ4‐immunonegative lingular zone (LZ; lobule I) and a striped anterior zone (AZ; lobules II–VIa) were distinguished. A central zone (CZ; ∼lobules VIa–VIIIa,b) and a posterior zone (PZ; ∼lobules VIIIa,b–IXc,d) were distinguished in the posterior lobe. Finally, the nodular zone (NZ; lobule X) is uniformly zebrin II‐immunoreactive and is innervated by vestibular mossy fibers. Lobule IXc,d is considered as a transitional region between the PZ and the NZ, because the vestibular mossy fiber projection extends into these lobules and because they receive optokinetic mossy and climbing fiber input. It is proposed that the zebrin II‐immunonegative P3‐ stripe corresponds to the lateral vermal B zone of the mammalian cerebellum and that the border between the avian homologs of the mammalian vermis and hemispheres is located immediately lateral to P3−. Thus, there seem to be transverse zones in chicken that are plausible homologs of those identified in mammals, together with an LZ that is characteristic of birds. J. Comp. Neurol. 518:2221–2239, 2010. © 2010 Wiley‐Liss, Inc.     

Purkinje cell compartmentation of the cerebellum of microchiropteran bats

Transverse boundaries divide the mammalian cerebellar cortex into transverse zones, and within each zone the cortex is further subdivided into a symmetrical array of parasagittal stripes. This topography is highly conserved across the Mammalia. Bats have a remarkable cerebellum with presumed adaptations to flight and to echolocation, but nothing is known of its compartmentation. We have therefore used two Purkinje cell compartmentation antigens, zebrin II/aldolase C and phospholipase Cβ4, to reveal the topography of the cerebellum in microchiropteran bats. Three species of bat were studied, Lasiurus cinereus, Lasionycteris noctivagans, and Eptesicus fuscus. A reproducible pattern of zones and stripes was revealed that is similar across the three species. The architecture of the bat cerebellum conforms to the ground plan of other mammals. However, two exceptions to the highly conserved mammalian architectural plan were revealed. First, many Purkinje cells in lobule I express zebrin II. A zebrin II‐immunopositive lobule I has not been seen previously in mammals but is characteristic of the avian cerebellum. Second, lobules VI–VII comprise the large central zone. Within the central zone two subdomains are evident, a small anterior subdomain (lobule VI) in which Purkinje cells are predominantly zebrin II‐immunopositive/PLCβ4‐immunonegative, as in other mammals, and a posterior subdomain (lobule VII), in which alternating zebrin II/phospholipase Cβ4 stripes are prominent. J. Comp. Neurol. 517:193–209, 2009. © 2009 Wiley‐Liss, Inc.     

Neurofilament Heavy Chain Expression Reveals a Unique Parasagittal Stripe Topography in the Mouse Cerebellum

Despite the general uniformity in cellular composition of the adult cerebellum (Cb), the expression of proteins such as ZebrinII/AldolaseC and the small heat shock protein HSP25 reveal striking patterns of parasagittal Purkinje cell (PC) stripes. Based on differences in the stripe configuration within subsets of lobules, the Cb can be further divided into four anterior–posterior transverse zones: anterior zone (AZ) = lobules I–V, central zone (CZ) = lobules VI–VII, posterior zone (PZ) = lobules VIII and anterior IX, and the nodular zone (NZ) = lobules posterior IX–X. Here we used whole-mount and tissue section immunohistochemistry to show that neurofilament heavy chain (NFH) expression alone divides all lobules of the mouse Cb into a complex series of parasagittal stripes of PCs. We revealed that the striped pattern of NFH in the vermis of the AZ and PZ was complementary to ZebrinII and phospholipase C ?3 (PLC?3), and corresponded to phospholipase C ?4 (PLC?4). In the CZ and NZ the stripe pattern of NFH was complementary to HSP25 and corresponded to PLC?3. The boundaries of the NFH stripes were not always sharply delineated. Instead, a gradual decrease in NFH expression was observed toward the edges of particular stripes, resulting in domains comprised of overlapping expression patterns. Furthermore, the terminal field distributions of mossy and climbing fibers had a complex but consistent topographical alignment with NFH stripes. In summary, NFH expression reveals an exquisite level of Cb stripe complexity that respects the transverse zone divisions and delineates an intricately patterned target field for Cb afferents.     

Selective Purkinje cell ectopia in the cerebellum of the weaver mouse

The adult mouse cerebellar vermis consists of four transverse zones, each of which is further subdivided into parasagittal stripes. In the adult weaver (wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is abnormal, consistent with the absence of a central zone (approximately lobules VI/VII). Because the small, heat shock protein HSP25 is a constitutive marker of parasagittal bands of Purkinje cells in the caudal central zone and the nodular zone (approximately lobules IX/X), we used HSP25 immunocytochemistry to show that the patterning abnormalities in wv/wv reflect selective Purkinje cell ectopia rather than the absence of the central zone. A specific HSP25-immunopositive Purkinje cell ectopia within the central zone was identified. Symmetrical clusters of HSP25-immunopositive Purkinje cells, which presumably would have formed the parasagittal stripes in the wild type, are present ectopically on either side of the midline in wv/wv. In contrast, in the nodular zone, HSP25-immunopositive Purkinje cells form a near-monolayer and are organized into parasagittal stripes. We therefore conclude that specific Purkinje cell clusters in the wv/wv cerebellum fail to disperse and that this ectopia contributes to the topographical abnormalities.     

Expression of heat-shock protein Hsp25 in mouse Purkinje cells during development reveals novel features of cerebellar compartmentation

The small heat shock protein Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal stripes of Purkinje cells confined to the caudal central zone ( approximately lobules VI and VII), the nodular zone ( approximately ventral lobule IX and lobule X), and the paraflocculi/flocculi. During development several distinct phases in Hsp25 expression can be distinguished. Hsp25-immunopositive Purkinje cells are first seen at birth, when four clusters are visible in the vermis of lobules IV/V, and scattered Hsp25-immunoreactive Purkinje cells are seen in lobule VIII. By postnatal day 2/3, six narrow parasagittal stripes of Hsp25-immunopositive Purkinje cells are seen in the vermis of the anterior lobe. In the posterior lobules, most Purkinje cells in the vermis of lobules VIII and IX express Hsp25. This initial limited expression is followed by a phase of widespread expression (postnatal days 6-9) in which Hsp25 immunoreactivity is detected in virtually all Purkinje cells. This global cerebellar expression of Hsp25 then gradually disappears, first in the anterior zone and the hemispheres and subsequently in the posterior zone, to leave the restricted adult expression pattern. Western blotting analysis and immunoprecipitation with anti-Hsp25 suggest that all immunocytochemistry can be attributed the expression of Hsp25. Furthermore, visual deprivation had no effect on the development of Hsp25 expression in Purkinje cells, suggesting that visuomotor input is not responsible for the establishment of constitutive Hsp25 expression in the cerebellar cortex.     

Complementary stripes of phospholipase Cbeta3 and Cbeta4 expression by Purkinje cell subsets in the mouse cerebellum

Transverse boundaries divide the cerebellar cortex into four transverse zones, and within each zone the cortex is further subdivided into a symmetrical array of parasagittal stripes. Several molecules believed to mediate long-term depression at the parallel fiber-Purkinje cell synapse are known to be expressed in stripes. We have therefore explored the distributions of phospholipase Cbeta3 and phospholipase Cbeta4, key components in the transduction of type 1 metabotropic glutamate receptor-mediated responses. The data reveal that both phospholipase Cbeta isotypes are expressed strongly in the mouse cerebellum in subsets of Purkinje cells. The two distributions are distinct and largely nonoverlapping. The pattern of phospholipase Cbeta3 expression is unique, revealing stripes in three of the four transverse zones and a uniform distribution in the fourth. In contrast, phospholipase Cbeta4 appears to be confined largely to the Purkinje cells that are phospholipase Cbeta3-negative. PLCbeta3 is restricted to the zebrin II-immunopositive Purkinje cell subset. Not all zebrin II-immunoreactive Purkinje cells express PLCbeta3: in lobules IX and X it is restricted to that zebrin II-immunopositive subset that also expresses the small heat shock protein HSP25. PLCbeta4 expression is restricted to, and coextensive with, the zebrin II-immunonegative Purkinje cell subset. These nonoverlapping expression patterns suggest that long-term depression may be manifested differently between cerebellar modules.     

Antigenic compartmentation of the cerebellar cortex in the syrian hamster Mesocricetus auratus

Despite the apparent uniformity in cellular composition of the adult cerebellar cortex, a complex heterogeneous pattern can be revealed by using biochemical markers. One example is zebrin II/aldolase C, which is expressed by a subset of Purkinje cells that form a highly reproducible array of stripes. Zebrin II/aldolase C immunohistochemistry has been used in both section and whole mount preparations to analyze the architecture of the hamster cerebellar cortex. As in other species studied, zebrin II immunoreactivity in the hamster cerebellum is restricted to a subset of Purkinje cells and, more weakly, to astrocytes. Based on the distribution of these Purkinje cell subsets the hamster cerebellar vermis was found to consist of four transverse zones-the anterior zone, central zone, posterior zone and nodular zone. Zebrin II/aldolase C is expressed uniformly in the central and nodular zones, and as parasagittal stripes in the anterior and central zones. A similar alternation of homogeneous and striped expression domains is seen in the hemispheres. The topography of the hamster cerebellar cortex as revealed by zebrin II expression domains closely resembles that reported in other mammals. Thus, a cerebellar zone-and-stripe topography appears to be conserved across the Mammalia.     

Development of Hsp25 expression compartments is not constrained by Purkinje cell defects in the Lurcher mouse mutant

Four transverse zones can be distinguished in the adult mouse cerebellar cortex based on differential expression of cell-specific antigens, termination patterns of mossy fiber afferents, and phenotypes of mouse mutants with cerebellar defects: the anterior zone (AZ), central zone (CZ), posterior zone (PZ), and nodular zone (NZ). In the heterozygous Lurcher (Lc/+) mouse a zonally restricted abnormality in Purkinje cell development is seen. The Purkinje cell-specific antigen zebrin II is normally differentially expressed in all four zones of the adult cerebellum, but in the Lc/+ mutant is confined to the PZ and NZ, caudal to a transverse boundary in the dorsal aspect of lobule VIII. In this study we wanted to understand why zebrin II expression is arrested at this boundary and whether the Lc mutation affects the differentiation of additional Purkinje cell antigens in a similar manner. To determine this, we took advantage of the dynamic developmental timetable of another Purkinje cell antigen, the small heat shock protein Hsp25. Using immunohistochemistry we demonstrate that cerebellar maturation anterior to the CZ/PZ transverse boundary appears to be unaffected by the Lc allele, in that initial progression of Hsp25 expression in the Lc/+ cerebellum was similar to controls. Double-labeling experiments with anti-Hsp25 and anti-calbindin suggest that characteristic banding patterns of Hsp25 in Lc/+ cerebellum develop and are preserved despite cell loss. Thus, since simple temporal or spatial models cannot account for the zonal restriction seen during Lc/+ cerebellar development, the abnormality may be zebrin II-specific.     

Heat shock protein 25 expression and preferential Purkinje cell survival in the lurcher mutant mouse cerebellum

The spatial organization of the mouse cerebellum into transverse zones and parasagittal stripes is reflected during the temporal progression of Purkinje cell death in the Lurcher mutant mouse (+/Lc). Neurodegeneration in the +/Lc mutant is apparent by the second postnatal week and is initially seen in all four transverse zones: the anterior (lobules I–V), central (lobules VI, VII), posterior (lobules VIII, dorsal IX), and nodular (ventral lobule IX and lobule X) zone. However, from postnatal day (P)25–P36, Purkinje cell loss proceeds more rapidly in the anterior zone, followed by the posterior and central zones, and is significantly delayed in the nodular zone. Coronal sections through the +/Lc cerebellum reveal that surviving Purkinje cells are restricted to the paraflocculus/flocculus and the nodular zone and could be detected as late as P146 (∼5 months). Within this region, the pattern of preferentially surviving calbindin‐immunoreactive Purkinje cells reflects the expression of the constitutively expressed small heat shock protein HSP25 in the wild‐type cerebellum. Although the role of constitutively expressed HSP25 in the wild‐type cerebellum is not clear, it appears to play a neuroprotective role in the flocculonodular region of the +/Lc mutant cerebellum as the percentage of surviving Purkinje cells that are HSP25‐immunopositive significantly increases over time. J. Comp. Neurol. 518:1892–1907, 2010. © 2009 Wiley‐Liss, Inc.     

Regionalization defects in the weaver mouse cerebellum

The mammalian cerebellum consists of parasagittal bands and transverse zones that are laid down early in development. When the adult cerebellum is immunostained for the Purkinje cell-specific antigen zebrin II (i.e., aldolase C), compartmentation is reflected in alternating zebrin II⁺ (P⁺) and zebrin II⁻ bands (P⁻). The zebrin II phenotype is Purkinje cell autonomous; thus, disruptions in the zebrin pattern may reflect early problems in pattern formation. Zebrin II expression has been examined in the weaver (wv) mouse cerebellum. Both zebrin II⁺ and zebrin II⁻ Purkinje cells are present in the homozygous weaver (wv/wv) mouse, but they are not distributed normally. In the posterior vermis, although the zebrin II⁺ bands are wider and multilaminate, the standard compartmentation is present. However, a large zebrin II⁺ cell mass is absent from the central vermis, and analysis of the anterior lobe reveals several missing zebrin II⁺ bands. The cytoarchitectonic defects in wv mice are not simply related to the Purkinje cell abnormalities. Instead, serial reconstruction reveals two transverse boundaries—one rostrally in lobule VI and the other caudally in lobule IX—that delineate cytoarchitectonic transverse zones important in cerebellar development. The abnormal zebrin expression pattern in wv/wv mice may be secondary to the deletion of a transverse zone. This is the first demonstration that Purkinje cell compartmentation can be altered by mutation; therefore, the wv mutation should prove valuable in understanding cerebellar regionalization. J. Comp. Neurol. 394:431–444, 1998. © 1998 Wiley-Liss, Inc.     

Compartmentation of the rabbit cerebellar cortex

The cytoarchitecture of the adult rabbit cerebellum is revealed by using zebrin II/aldolase c immunocytochemistry in both wholemount and sectioned material. Zebrin II is expressed by approximately half of the Purkinje cells of the cerebellar cortex. In most regions these form a symmetrical array of zebrin II positive and negative parasagittal bands. Four transverse expression domains are identified in the vermis: (1) an anterior zone, comprising four narrow bands, one at the midline and three laterally to either side, extending throughout the anterior lobe to the primary fissure; (2) a central zone with broad immunoreactive bands separated by narrow zebrin II negative bands that disappear caudally to leave no apparent compartmentation; (3) a posterior zone with prominent alternating zebrin II positive and negative bands; and (4) a nodular zone in which all Purkinje cells express zebrin II. In the hemispheres a striped topography is found in lobules HVI, HVII, and crus I, and all Purkinje cells are zebrin II+ in the flocculus and paraflocculus. Because of its importance for the classical conditioning of the eyeblink response, we made a detailed analysis of lobule HVI of the hemisphere. The immunocytochemical data show a complex substructure within HVI with three prominent zebrin II positive bands (probably homologous with P4a+, P4b+, and P5+ of rodents) separated by two zebrin II negative regions (P4- and P4b-). Thus, the organization of the rabbit cerebellum is consistent with the patterns described previously for rat, mouse, and opossum and suggests that there may be a common ground plan for the mammalian cerebellum.     

Compartmentation of gaba b receptor2 expression in the mouse cerebellar cortex

Despite the apparent uniformity in cellular composition of the adult mammalian cerebellar cortex, it is actually highly compartmentalized into transverse zones, and within each zone the cortex is further subdivided into a reproducible array of parasagittal stripes. The most extensively studied compartmentation antigen is zebrin II/aldolase c, which is expressed by a subset of Purkinje cells forming parasagittal stripes. Gamma-aminobutyric acid B receptors (GABABRs) are G-protein-coupled receptors that mediate a slow, prolonged form of inhibition in many brain areas. This study examines the localization of GABABR2 in the mouse cerebellum by using whole mount and section immunohistochemistry. The data reveal that GABABR2 immunoreactivity is expressed strongly in the dendrites of a subset of Purkinje cells that form a reproducible array of transverse zones and parasagittal stripes. By using double immunostaining, the striped pattern of GABABR2 expression was shown to be identical to that revealed by anti-zebrin II and complementary to that of phospholipase Cbeta4. This finding supports previous functional studies showing that inhibitory neurotransmission is highly patterned in the cerebellar cortex.     

Novel developmental boundary in the cerebellum revealed by zebrin expression in the lurcher (Lc/+) mutant mouse.

The cerebellar cortex contains at least two classes of Purkinje cells, which are organized into alternating arrays of parasagittal bands. The clearest demonstration of this compartmentation is the pattern of expression of a family of polypeptide antigens, the zebrins, which are expressed selectively by Purkinje cell subsets. Furthermore, anterograde tracing experiments show that the zebrin compartments are closely correlated with both afferent and efferent projection maps. The further subdivision of long parasagittal bands into smaller modules may occur through several different mechanisms, including the intrinsic cerebellar lobulation and the selective distribution of afferent terminal fields. However, while the longitudinal subdivisions are straightforwardly shown, the mediolateral boundaries are more subtle. In this report we describe a novel mediolateral and anteroposterior compartmentation boundary in mice, running across lobule VIII, that is revealed by the consequences of the lurcher (Lc/+) allele for zebrin expression. In normal mice zebrin compartmentation develops in several discrete stages: until postnatal day 5 (PD5) there is no zebrin expression; from PD5-PD7 zebrin is found only in the posterior lobe vermis, with immunoreactive Purkinje cells in lobules X, IX, and VIII but not elsewhere; from PD7-PD12 most Purkinje cells in the vermis become zebrin+; from PD12-PD15 immunoreactivity also appears in the hemispheres so that almost all Purkinje cells now are zebrin+; and finally, from PD15-PD25 zebrin is gradually suppressed in those Purkinje cells that are zebrin- in the adult until the mature pattern of parasagittal compartments is revealed. In the Lc/+ mutant the normal developmental progression is interrupted at around PD7. As a result, the pattern of zebrin expression becomes frozen at that stage when immunoreactive Purkinje cells are confined exclusively to the posterior lobe vermis. A reproducible boundary between expressing and nonexpressing zones runs mediolaterally across the dorsal surface of lobule VIII. Apart from zebrin expression itself, there are no obvious structural correlates of this transition. This mediolateral boundary identifies a developmental unit in the posterior lobe vermis of the cerebellum, and provides further evidence that the cerebellum is a highly heterogeneous structure.     

Compartmentation of the mouse cerebellar cortex by neuronal calcium sensor-1

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. The detailed distribution of NCS-1 was analyzed in the mouse cerebellar cortex. In coronal sections, the NCS-1 immunostaining displayed characteristic parasagittal banding pattern in the Purkinje cell layer and molecular layer, while there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate-basket cells were uniformly NCS-1-positive throughout the cerebellum. Immunofluorescent double staining showed that NCS-1 and zebrin II exhibited a similar parasagittal banding pattern. Then, we performed mapping of NCS-1- and/or zebrin II-labeled Purkinje cell somata using seven sequential coronal sections. NCS-1-positive/zebrin II-positive Purkinje cell clusters were seen throughout the cerebellum, but NCS-1-positive/zebrin II-negative Purkinje cells were exceedingly rare. On the other hand, NCS-1-negative/zebrin II-positive Purkinje cell clusters were found in anterior lobule vermis and paraflocculus, whereas they were rarely seen in posterior lobules. The digitized quantitative analysis showed close relationship between NCS-1 and zebrin II immunoreactivity in the molecular layer. The correspondence between NCS-1 and zebrin II demonstrated here indicates a novel anteroposterior difference of cerebellar compartmentation and provides fundamental information of cerebellar organization.     

Topographical anatomy of the cerebellum in the guinea pig,Cavia porcellus

Zebrin II/aldolase C is expressed in a stereotyped array of parasagittal bands and transverse zones in the cerebellum of many animals including birds and mammals. Here, section and whole mount immunohistochemistry has been used to characterize the expression of zebrin II in the cerebellum of the adult guinea pig. Purkinje cells in the adult guinea pig express zebrin II immunoreactivity at three different levels of intensity-high, medium and low. This expression pattern reveals an arrangement of parasagittal bands that are symmetrical about the midline and reproducible between individuals. The expression of zebrin II divides the vermis into four transverse expression domains from rostral to caudal: an anterior zone consisting of one zebrin II-immunoreactive band at the midline and at least three symmetrical bands laterally; a central zone, in which broad zebrin II-positive bands are separated by narrow bands of zebrin II-negative Purkinje cells that disappear caudally to leave no overt compartmentation; a posterior zone consisting of alternating bands of zebrin II-positive and -negative Purkinje cells; and finally, a nodular zone in which nearly all Purkinje cells express zebrin II. In the anterior and posterior hemispheres, zebrin II is also expressed in a banded pattern. These rostrocaudal and mediolateral patterns of zebrin II expression are reminiscent of those in other mammals including rabbit, rat, and mouse, and suggest that there may be a fundamental compartmental organization of the cerebellum that is conserved in mammals.     

Abnormal dispersion of a purkinje cell subset in the mouse mutant cerebellar deficient folia (cdf).

Purkinje cells of different molecular phenotypes subdivide the cortex of the cerebellum both rostrocaudally into parasagittal bands and mediolaterally into transverse zones. Superimposed on the Purkinje cell compartmentation, the cerebellar cortex is pleated into a reproducible array of lobes and lobules. During cerebellar development, Purkinje cell bands are formed through the rostrocaudal dispersal of embryonic clusters, triggered primarily by a Reelin-dependent signaling pathway. In the naturally occurring mouse mutant cerebellar deficient folia (cdf), there is a failure of Purkinje cell dispersion that results in widespread Purkinje cell ectopia in the adult. The ectopia is restricted primarily to that subset of Purkinje cells that does not express zebrin II/aldolase C and that forms ectopic clusters in among the cerebellar nuclei. Most Purkinje cells that express zebrin II are located normally in a monolayer. Thus, the cerebellum of cdf mutants has a failure of Purkinje cell dispersion that is confined primarily to a zebrin II-negative (zebrin II(-)) subpopulation. Despite the Purkinje cell ectopia, the parasagittal band organization of the cerebellum is still clear. The shortening of the cortex is distributed evenly over all lobules, with the result that transverse expression boundaries are relocated with respect to the lobules and fissures. The number of Purkinje cells in the cdf/cdf cerebellum is similar to the number in littermate controls. Therefore, it appears that the lesion in cdf results in the failure of a zebrin II(-) Purkinje cell subset to disperse either due to a cell intrinsic defect or due to an abnormal interaction between the Purkinje cells and either granule cells or afferent inputs.     

Spatial rearrangement of Purkinje cell subsets forms the transverse and longitudinal compartmentalization in the mouse embryonic cerebellum

Transversely oriented lobules and longitudinally arrayed stripes of Purkinje cell subsets subdivide the cerebellar cortex into multiple compartments that are involved in diverse functions. In the mammalian cerebellum, anterior, and posterior lobules, which are involved in somatosensorimotor function, show an alternation of aldolase C (zebrin II) ‐positive and ‐negative stripes, whereas the central lobules (lobules VIb–VII and crus I), which are implicated in nonmotor functions, show a laterally expanded arrangement solely of aldolase C‐positive stripes. To understand the developmental process of this compartmental pattern, we identified groups of Purkinje cell subsets in the entire mouse cerebellum at embryonic day (E) 14.5 by staining Purkinje cell subset markers. We then tracked four major domains of Protocadherin 10 (Pcdh10)‐positive Purkinje cell subsets (medial, dorsal, central, and mid‐lateral subsets), which were clearly demarcated during E14.5–17.5. These domains of Purkinje cell subsets shifted predominantly in the longitudinal direction to be positioned in the anterior and posterior lobules. However, a particular portion of the medial and mid‐lateral domains, and the whole of the central domain shift in the lateral direction to be positioned in the central lobules. The results indicate that while the longitudinal shift of domains of Purkinje cell subsets forms the longitudinally striped compartments in the anterior and posterior cerebellum, the lateral shift of particular domains of Purkinje cell subsets underlies the laterally expanded arrangement of stripes in central lobules. Thus, the rearrangement of Purkinje cell subsets in the embryonic cerebellum is critically related to the compartmental organization in the mammalian cerebellum.