The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development
MetadataShow full item record
© 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.
Showing items related by title, author, creator and subject.
Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd proteins which influence the long-term positioning and dendritic maturation of cerebral cortical neuronsGladwyn-Ng, I.; Huang, L.; Ngo, L.; Li, S.; Qu, Z.; Vanyai, H.; Cullen, H.; Davis, J.; Heng, Julian (2016)© 2016 Gladwyn-Ng et al. Background: The development of neural circuits within the embryonic cerebral cortex relies on the timely production of neurons, their positioning within the embryonic cerebral cortex as well as ...
De Novo Mutations in DENR Disrupt Neuronal Development and Link Congenital Neurological Disorders to Faulty mRNA Translation Re-initiationHaas, M.; Ngo, L.; Li, S.; Schleich, S.; Qu, Z.; Vanyai, H.; Cullen, H.; Cardona-Alberich, A.; Gladwyn-Ng, I.; Pagnamenta, A.; Taylor, J.; Stewart, H.; Kini, U.; Duncan, K.; Teleman, A.; Keays, D.; Heng, Julian (2016)© 2016 The Author(s). Disruptions to neuronal mRNA translation are hypothesized to underlie human neurodevelopmental syndromes. Notably, the mRNA translation re-initiation factor DENR is a regulator of eukaryotic translation ...
TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neuronsNgo, L.; Haas, M.; Qu, Z.; Li, S.; Zenker, J.; Teng, K.; Gunnersen, J.; Breuss, M.; Habgood, M.; Keays, D.; Heng, Julian (2014)© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com. The microtubule cytoskeleton is critical for the generation and maturation of ...