The transcriptional repressor RP58 is crucial for cell-division patterning and neuronal survival in the developing cortex

The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterni...

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Bibliographic Details
Published in:Developmental biology 2009-07, Vol.331 (2), p.140-151
Main Authors: Okado, Haruo, Ohtaka-Maruyama, Chiaki, Sugitani, Yoshinobu, Fukuda, Yuko, Ishida, Reiko, Hirai, Shinobu, Miwa, Akiko, Takahashi, Akiyo, Aoki, Katsunori, Mochida, Keiji, Suzuki, Osamu, Honda, Takao, Nakajima, Kazunori, Ogawa, Masaharu, Terashima, Toshio, Matsuda, Junichiro, Kawano, Hitoshi, Kasai, Masataka
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Cell Differentiation - physiology
Cell Division - physiology
Cell Movement - physiology
Cell-cycle exit
Cerebral cortex
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Cerebral Cortex - physiology
Hippocampus - cytology
Hippocampus - embryology
Hippocampus - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Neurogenesis - physiology
Neurons - cytology
Neurons - physiology
Progenitor cell
Repressor Proteins - genetics
Repressor Proteins - physiology
RP58
Stem Cells - cytology
Stem Cells - physiology
Transcriptional repressor
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Summary:The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterning process, its details are not well understood. Here, we show that, in the developing cerebral cortex, the RP58 transcription repressor protein was expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons. Targeted deletion of the RP58 gene led to dysplasia of the neocortex and of the hippocampus, reduction of the number of mature cortical neurons, and defects of laminar organization, which reflect abnormal neuronal migration within the cortical plate. We demonstrate an impairment of the cell-division patterning during the late embryonic stage and an enhancement of apoptosis of the postmitotic neurons in the RP58-deficient cortex. These results suggest that RP58 controls cell division of progenitor cells and regulates the survival of postmitotic cortical neurons.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2009.04.030