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.
Armstrong
Carol L
CL
Department of Cell Biology & Anatomy, Genes and Development Research Group, Hotchkiss Brain Institute, Faculty of Medicine, The University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Vogel
M W
MW
Hawkes
Richard
R
D000818:Animals; D064026:Calbindins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006579:Heterozygote; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064026:Calbindins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; C071871:zebrin II