
Ablation of astrocytes disrupts development of other cell types of the cerebellum. Cerebella of nontransgenic mice were treated with GCV at P1 [a, e, i, m (column 1)], or transgenic mice were treated at either P1 [b, f, j, n (column 2)], P3 [c, g, k, o (column 3)], or P5 [d, h, l, p (column 4)]. a–d, Low-power H&E paraffin sections show overall reduction in size of cerebellum of transgenic versus nontransgenic mice treated with GCV on P1, P3, or P5, with decreasing severity the later the treatment.e–h, H&E paraffin sections show loss of granule cells in transgenic mice. The Purkinje cells fail to align in a single layer in the animals treated at P1, and there is no distinct molecular layer. Both the granule cell loss and Purkinje cell disorganization become gradually less severe in animals treated at P3 and P5.i–l, GFAP immunocytochemistry displays disorganized radial Bergmann glia (especially in animals treated at P1) and apparent increase in GFAP immunoreactivity in animals treated at P3 and P5.m–p, Calbindin immunocytochemistry illustrates aberrant Purkinje cell dendritic morphology. In animals treated at P1, the dendrites project randomly rather than toward the pial surface. In animals treated at P3 or P5, the Purkinje cell primary dendrite projects toward the pial surface, but dendritic tree seems simplified, and many distal branches curve back and away from the pial surface (“weeping willow,” arrow in o). Scale bars: a–d, 500 μm; e–p, 100 μm.




