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Article

Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs

Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA
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Academic Editor: Alexander E. Kalyuzhny
Cells 2021, 10(2), 253; https://doi.org/10.3390/cells10020253
Received: 7 December 2020 / Revised: 16 January 2021 / Accepted: 21 January 2021 / Published: 28 January 2021
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Neocortical Circuit Formation)
Extrinsic molecules such as morphogens can regulate timed mRNA translation events in developing neurons. In particular, Wingless-type MMTV integration site family, member 3 (Wnt3), was shown to regulate the translation of Foxp2 mRNA encoding a Forkhead transcription factor P2 in the neocortex. However, the Wnt receptor that possibly mediates these translation events remains unknown. Here, we report Frizzled member 7 (Fzd7) as the Wnt3 receptor that lays downstream in Wnt3-regulated mRNA translation. Fzd7 proteins co-localize with Wnt3 ligands in developing neocortices. In addition, the Fzd7 proteins overlap in layer-specific neuronal subpopulations expressing different transcription factors, Foxp1 and Foxp2. When Fzd7 was silenced, we found decreased Foxp2 protein expression and increased Foxp1 protein expression, respectively. The Fzd7 silencing also disrupted the migration of neocortical glutamatergic neurons. In contrast, Fzd7 overexpression reversed the pattern of migratory defects and Foxp protein expression that we found in the Fzd7 silencing. We further discovered that Fzd7 is required for Wnt3-induced Foxp2 mRNA translation. Surprisingly, we also determined that the Fzd7 suppression of Foxp1 protein expression is not Wnt3 dependent. In conclusion, it is exhibited that the interaction between Wnt3 and Fzd7 regulates neuronal identity and the Fzd7 receptor functions as a downstream factor in ligand Wnt3 signaling for mRNA translation. In particular, the Wnt3-Fzd7 signaling axis determines the deep layer Foxp2-expressing neurons of developing neocortices. Our findings also suggest that Fzd7 controls the balance of the expression for Foxp transcription factors in developing neocortical neurons. These discoveries are presented in our manuscript within a larger framework of this review on the role of extrinsic factors in regulating mRNA translation. View Full-Text
Keywords: neocortical development; ligand Wnt3 signaling; Fzd7 receptor; Foxp transcription factor; mRNA translation regulation; morphogen factor neocortical development; ligand Wnt3 signaling; Fzd7 receptor; Foxp transcription factor; mRNA translation regulation; morphogen factor
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MDPI and ACS Style

Park, Y.; Lofton, M.; Li, D.; Rasin, M.-R. Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs. Cells 2021, 10, 253. https://doi.org/10.3390/cells10020253

AMA Style

Park Y, Lofton M, Li D, Rasin M-R. Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs. Cells. 2021; 10(2):253. https://doi.org/10.3390/cells10020253

Chicago/Turabian Style

Park, Yongkyu, Midori Lofton, Diana Li, and Mladen-Roko Rasin. 2021. "Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs" Cells 10, no. 2: 253. https://doi.org/10.3390/cells10020253

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