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Expression and regulation of the LIM‐class homeobox gene rlim‐1 in neuronal progenitors of the rat cerebellum
Author(s) -
Hayes William Par,
Yangco Nathaniel,
Chin Hemin,
Mill John F.,
Pu Le Ping,
Taira Masanori,
Dawid Igor B.,
Gallo Vittorio
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20010201)63:3<237::aid-jnr1017>3.0.co;2-4
Subject(s) - biology , granule (geology) , microbiology and biotechnology , messenger rna , cerebellum , gene , biochemistry , neuroscience , paleontology
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. J. Neurosci. Res. 63:237–251, 2001. Published 2001 Wiley‐Liss, Inc.