Expression and regulation of the LIM-class homeobox gene rlim-1 in neuronal progenitors of the rat cerebellum.
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 vivo 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 showed that expression was also maximal at p8. In situ hybridization showed that 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 staining demonstrated that at p8 rlim-1 protein was also present in proliferative 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 protein was detected in migratory granule neurons. The developmental decrease in rlim-1 mRNA and protein found in vivo was reproduced in pure cerebellar granule cell cultures. In these cultures, granule neurons were postmitotic 1 day after plating but still displayed high levels of rlim-1 protein expression 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 expression in granule neurons is regulated autonomously, and 3) rlim-1 protein may also play an important role in granule neuron differentiation and survival. Published 2001 Wiley-Liss, Inc.
Hayes
W P
WP
Department of Biology, Catholic University of America, Washington, DC, USA.
Yangco
N
N
Chin
H
H
Mill
J F
JF
Pu
L P
LP
Taira
M
M
Dawid
I B
IB
Gallo
V
V
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002525:Cerebellar Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases
D018076:DNA, Complementary; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499522:Lhx1 protein, rat; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C492371:Rlim protein, rat; D044767:Ubiquitin-Protein Ligases