B. Kuemerle et al., PATTERN DEFORMITIES AND CELL LOSS IN ENGRAILED-2 MUTANT MICE SUGGEST 2 SEPARATE PATTERNING EVENTS DURING CEREBELLAR DEVELOPMENT, The Journal of neuroscience, 17(20), 1997, pp. 7881-7889
Null alleles of the mouse Engrailed-2 gene, a molecular homolog of the
fly gene engrailed, have demonstrable effects on the anteroposterior
(A/P) patterning of cerebellum as reflected in the disruption of the n
ormal process of foliation of the cerebellar cortex and the alteration
of transgene expression boundaries in the adult. Engrailed-2 also aff
ects the transient mediolateral (M/L) pattern of En-1 and Wnt-7b expre
ssion seen in late embryogenesis. We have examined three markers of ce
rebellar compartmentation in En-2 mutant mice: the Zebrin II and Ppath
monoclonal antibodies and the transgene L7lacZ. In En-2 mutants, the
normal temporal pattern of expression is preserved for all three marke
rs, although the size and spatial location of various bands differ fro
m those of the wild type. Unlike the foliation abnormalities, the M/L
pattern disturbances we have found occur in nearly all cerebellar regi
ons. Cell counts reveal that all major cell types of the olivocerebell
ar circuit are reduced by 30-40%. We propose that these results are be
st explained by a model in which the Engrailed-2 gene is involved in t
he early specification of the cerebellar field including the number of
progenitors. Because each of these progenitors gives rise to a clone
of defined size, Engrailed-2 helps specify adult cell number. We furth
er postulate that the configuration of the seven Zebrin bands as well
as the shapes and locations of the cerebellar lobules are set up by a
second patterning event that occurs after neurogenesis is complete.