NDLI: Purkinje cell compartmentalization in the cerebellum of the spontaneous mutant mouse dreher

Content Provider	Springer Nature Link
Author	Sillitoe, Roy V. George Jones, Nicholas A. Millen, Kathleen J. Hawkes, Richard
Copyright Year	2012
Abstract	The cerebellar morphological phenotype of the spontaneous neurological mutant mouse dreher (Lmx1a dr-J ) results from cell fate changes in dorsal midline patterning involving the roof plate and rhombic lip. Positional cloning revealed that the gene Lmx1a, which encodes a LIM homeodomain protein, is mutated in dreher, and is expressed in the developing roof plate and rhombic lip. Loss of Lmx1a causes reduction of the roof plate, an important embryonic signaling center, and abnormal cell fate specification within the embryonic cerebellar rhombic lip. In adult animals, these defects result in variable, medial fusion of the cerebellar vermis and posterior cerebellar vermis hypoplasia. It is unknown whether deleting Lmx1a results in displacement or loss of specific lobules in the vermis. To distinguish between an ectopic and absent vermis, the expression patterns of two Purkinje cell-specific compartmentation antigens, zebrin II/aldolase C and the small heat shock protein HSP25 were analyzed in dreher cerebella. The data reveal that despite the reduction in volume and abnormal foliation of the cerebellum, the transverse zones and parasagittal stripe arrays characteristic of the normal vermis are present in dreher, but may be highly distorted. In dreher mutants with a severe phenotype, zebrin II stripes are fragmented and distributed non-symmetrically about the cerebellar midline. We conclude that although Purkinje cell agenesis or selective Purkinje cell death may contribute to the dreher phenotype, our data suggest that aberrant anlage patterning and granule cell development lead to Purkinje cell ectopia, which ultimately causes abnormal cerebellar architecture in dreher.
Starting Page	35
Ending Page	47
Page Count	13
File Format	PDF
ISSN	18632653
Journal	Anatomy and Embryology
Volume Number	219
Issue Number	1
e-ISSN	18632661
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2012-11-18
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Whole-mount immunohistochemistry HSP25 Zebrin II Cerebellar development Lmx1a Neurosciences Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Anatomy Histology

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