Wp. Hayes et al., Expression and regulation of the LIM-class homeobox gene rlim-1 in neuronal progenitors of the rat cerebellum, J NEUROSC R, 63(3), 2001, pp. 237-251
To investigate LIM gene function in the rat cerebellar system, we analyzed
expression and regulation of the rat homologue of frog Xlim-1 (rlim-1) in v
ivo and in cultured cells. In developing cerebellum, peak levels of rlim-1
mRNA at postnatal day 8 (p8) are coincident with the peak period of granule
cell proliferation. Analysis of rlim-1 protein with a specific antibody sh
owed that expression was also maximal at p8, In situ hybridization showed t
hat at p8 rlim-1 mRNA was expressed in Purkinje and granule cells. Both the
proliferative and the premigratory granule cells in the external germinal
zone displayed high levels of rlim-1 mRNA expression. Immunocytochemical st
aining demonstrated that at p8 rlim-1 protein was also present in prolifera
tive and premigratory granule cells, In adult cerebellum (p30), rlim-1 mRNA
and protein expression in granule cells was strongly attenuated. The down-
regulation of rlim-1 mRNA occurred in granule cells just after the time of
final division, coinciding with the onset of their migration. rlim-1 protei
n was detected in migratory granule neurons. The developmental decrease in
rlim-1 mRNA and protein found in vivo was reproduced in pure cerebellar gra
nule cell cultures. In these cultures, granule neurons were postmitotic I d
ay after plating but still displayed high levels of rlim-1 protein expressi
on up to 3 days in vitro. Our findings indicate that 1) rlim-1 is likely to
act in concert with other genes to specify granule cell fate, 2) rlim-1 ex
pression in granule neurons is regulated autonomously, and 3) rlim-1 protei
n may also play an important role in granule neuron differentiation and sur
vival. Published 2001 Wiley-Liss, Inc.dagger