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Tumor‐suppressor p53 is expressed in proliferating and newly formed neurons of the embryonic and postnatal rat brain: Comparison with expression of the cell cycle regulators p21 Waf1/Cip1 , p27 Kip1 , p57 Kip2 , p16 Ink4a , cyclin G1, and the proto‐oncogene bax
Author(s) -
Lookeren Campagne Menno Van,
Gill Ramanjit
Publication year - 1998
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19980727)397:2<181::aid-cne3>3.0.co;2-x
Subject(s) - biology , cell cycle , olfactory bulb , microbiology and biotechnology , subventricular zone , embryonic stem cell , cyclin , forebrain , cyclin b1 , cyclin a , cyclin d , cell , neuroscience , central nervous system , cyclin dependent kinase 1 , stem cell , neural stem cell , biochemistry , genetics , gene
The tumor‐suppressor protein p53 has been implicated in cell cycle arrest and apoptotic cell death in dividing cells (Yonish‐Rouach et al. [1991] Nature 352:342–347). To elucidate possible functions of p53 in the regulation of cell division and cell death during development of the rat central nervous system, we compared the spatial and temporal expressions of p53 mRNA and protein with those of its transcriptional targets Bax, p21 Waf1 , and cyclin G1 and with the cyclin‐dependent kinase inhibitors p27 Kip1 , p57 Kip2 , and p16 Ink4a . From embryonic day 14 until the second postnatal week, p53 mRNA and protein were found predominantly in proliferating zones, including the cells of the emerging external granular layer of the cerebellum, and the ventricular and the subventricular zones of the forebrain. At all postnatal ages, there was a high expression of p53 mRNA and protein in cells of the rostral migratory stream, a well‐defined pathway along which precursor cells of olfactory interneurons migrate from the ventricular and subventricular zones toward the olfactory bulb. In addition to its expression in proliferating cell populations, p53 was expressed in postmitotic cells of the cerebral cortex and hippocampus at embryonic and early postnatal stages. p53, p27 Kip1 , p16 Ink4a , and bax α mRNA colocalized in the ventricular and subventricular zones at embryonic and early postnatal stages, but the distribution of p53 differed from that of its transcriptional targets cyclin G1 and p21 Waf1 and from that of the cyclin‐dependent kinase inhibitor p57 Kip2 , which were predominantly expressed in fully differentiated neurons. Double‐labeling studies showed that p53 mRNA and protein were absent in cells undergoing developmental cell death, as identified by the presence of single‐ or double‐stranded nuclear DNA breaks. Protein levels of p53 decreased during development in all brain areas studied. These results indicate a role for p53 in the control of cell division and early differentiation rather than in the control of cell death during rat brain development. The nonoverlapping temporal and spatial expression patterns of p53 and its transcriptional targets Bax, cyclin G1 and p21 Waf1 suggest that each of these gene products fulfill independent roles in brain morphogenesis. J. Comp. Neurol. 397:181–198, 1998. © 1998 Wiley‐Liss, Inc.