The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development
© 2013 The Author. The zinc finger transcription factor RP58 (also known as ZNF238) regulates neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et al. 2011; Baubet et al. 2012; Ohtaka-Maruyama et al. 2013), but its mechanism of action remains unclear. In this study, we rep...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Published: |
Oxford Uni Press Inc
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/72182 |
| _version_ | 1848762681824116736 |
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| author | Heng, Julian Qu, Z. Ohtaka-Maruyama, C. Okado, H. Kasai, M. Castro, D. Guillemot, F. Tan, S. |
| author_facet | Heng, Julian Qu, Z. Ohtaka-Maruyama, C. Okado, H. Kasai, M. Castro, D. Guillemot, F. Tan, S. |
| author_sort | Heng, Julian |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2013 The Author. The zinc finger transcription factor RP58 (also known as ZNF238) regulates neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et al. 2011; Baubet et al. 2012; Ohtaka-Maruyama et al. 2013), but its mechanism of action remains unclear. In this study, we report a cell-autonomous function for RP58 during the differentiation of embryonic cortical projection neurons via its activities as a transcriptional repressor. Disruption of RP58 expression alters the differentiation of immature neurons and impairs their migration and positioning within the mouse cerebral cortex. Loss of RP58 within the embryonic cortex also leads to elevated mRNA for Rnd2, a member of the Rnd family of atypical RhoA-like GTPase proteins important for cortical neuron migration (Heng et al. 2008). Mechanistically, RP58 represses transcription of Rnd2 via binding to a 3'-regulatory enhancer in a sequence-specific fashion. Using reporter assays, we found that RP58 repression of Rnd2 is competed by proneural basic helix-loop-helix transcriptional activators. Finally, our rescue experiments revealed that negative regulation of Rnd2 by RP58 was important for cortical cell migration in vivo. Taken together, these studies demonstrate that RP58 is a key player in the transcriptional control of cell migration in the developing cerebral cortex. |
| first_indexed | 2025-11-14T10:51:26Z |
| format | Journal Article |
| id | curtin-20.500.11937-72182 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:51:26Z |
| publishDate | 2015 |
| publisher | Oxford Uni Press Inc |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-721822018-12-13T09:33:30Z The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development Heng, Julian Qu, Z. Ohtaka-Maruyama, C. Okado, H. Kasai, M. Castro, D. Guillemot, F. Tan, S. © 2013 The Author. The zinc finger transcription factor RP58 (also known as ZNF238) regulates neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et al. 2011; Baubet et al. 2012; Ohtaka-Maruyama et al. 2013), but its mechanism of action remains unclear. In this study, we report a cell-autonomous function for RP58 during the differentiation of embryonic cortical projection neurons via its activities as a transcriptional repressor. Disruption of RP58 expression alters the differentiation of immature neurons and impairs their migration and positioning within the mouse cerebral cortex. Loss of RP58 within the embryonic cortex also leads to elevated mRNA for Rnd2, a member of the Rnd family of atypical RhoA-like GTPase proteins important for cortical neuron migration (Heng et al. 2008). Mechanistically, RP58 represses transcription of Rnd2 via binding to a 3'-regulatory enhancer in a sequence-specific fashion. Using reporter assays, we found that RP58 repression of Rnd2 is competed by proneural basic helix-loop-helix transcriptional activators. Finally, our rescue experiments revealed that negative regulation of Rnd2 by RP58 was important for cortical cell migration in vivo. Taken together, these studies demonstrate that RP58 is a key player in the transcriptional control of cell migration in the developing cerebral cortex. 2015 Journal Article http://hdl.handle.net/20.500.11937/72182 10.1093/cercor/bht277 Oxford Uni Press Inc restricted |
| spellingShingle | Heng, Julian Qu, Z. Ohtaka-Maruyama, C. Okado, H. Kasai, M. Castro, D. Guillemot, F. Tan, S. The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title | The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title_full | The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title_fullStr | The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title_full_unstemmed | The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title_short | The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development |
| title_sort | zinc finger transcription factor rp58 negatively regulates rnd2 for the control of neuronal migration during cerebral cortical development |
| url | http://hdl.handle.net/20.500.11937/72182 |