Persistent Lin28 Expression Impairs Neurite Outgrowth and Cognitive Function in the Developing Mouse Neocortex

Jang, Hyun‐Jong; Kim, Joo Youn; Kim, Seong Yun; Cho, Kyung-Ok

doi:10.1007/s12035-018-1297-0

Cited by 10 publications

(8 citation statements)

References 47 publications

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“…Lin28 is found in the cytoplasm and cytoplasmic bodies such as processing bodies and stress granules, and partially in the nucleus (Kawahara et al, 2012). While Lin28 is expressed in cell-renewing cells to promote cell proliferation, let7 is absent in stem cells (Rehfeld et al, 2015;Jang et al, 2019). Lin28B can be found in progenitor cells and the cerebral cortex whereas both Lin28A and Lin28B are expressed in neural progenitor cells expressing nestin and Pax6 in the ventricular and SVZ (Hennchen et al, 2015).…”

Section: Lin28mentioning

confidence: 99%

RNA-binding protein signaling in adult neurogenesis

Chan

Sánchez-Vidaña

Anoopkumar‐Dukie

et al. 2022

Front. Cell Dev. Biol.

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The process of neurogenesis in the brain, including cell proliferation, differentiation, survival, and maturation, results in the formation of new functional neurons. During embryonic development, neurogenesis is crucial to produce neurons to establish the nervous system, but the process persists in certain brain regions during adulthood. In adult neurogenesis, the production of new neurons in the hippocampus is accomplished via the division of neural stem cells. Neurogenesis is regulated by multiple factors, including gene expression at a temporal scale and post-transcriptional modifications. RNA-binding Proteins (RBPs) are known as proteins that bind to either double- or single-stranded RNA in cells and form ribonucleoprotein complexes. The involvement of RBPs in neurogenesis is crucial for modulating gene expression changes and posttranscriptional processes. Since neurogenesis affects learning and memory, RBPs are closely associated with cognitive functions and emotions. However, the pathways of each RBP in adult neurogenesis remain elusive and not clear. In this review, we specifically summarize the involvement of several RBPs in adult neurogenesis, including CPEB3, FXR2, FMRP, HuR, HuD, Lin28, Msi1, Sam68, Stau1, Smaug2, and SOX2. To understand the role of these RBPs in neurogenesis, including cell proliferation, differentiation, survival, and maturation as well as posttranscriptional gene expression, we discussed the protein family, structure, expression, functional domain, and region of action. Therefore, this narrative review aims to provide a comprehensive overview of the RBPs, their function, and their role in the process of adult neurogenesis as well as to identify possible research directions on RBPs and neurogenesis.

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Section: Lin28mentioning

confidence: 99%

RNA-binding protein signaling in adult neurogenesis

Chan

Sánchez-Vidaña

Anoopkumar‐Dukie

et al. 2022

Front. Cell Dev. Biol.

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“…These mRNA targets are mostly involved with the Igf2–mTOR signaling pathway that drives progenitor proliferation ( Hentges et al, 2001 ). Other studies have directly linked Lin28a function with translational regulation and cell division by showing that Lin28a silencing decreases the levels of its targets Hmga2 and Igf1r , whereas Lin28a OE upregulates Hmga2 and Igf2 in mouse primary cultures of electroporated cortical neurons ( Bhuiyan et al, 2013 ; Jang et al, 2019 ). Polysome profiling analysis of Lin28a/b KO embryonic neocortices indicated that transcripts associated with translation, ribosome biogenesis, mTOR pathway, and cell cycle are decreased, whereas transcripts involved with neuronal differentiation are significantly upregulated in double mutants.…”

Section: Post-transcriptional Regulation Mrnas Poised For Translation and Rna-binding Proteinsmentioning

confidence: 99%

“…Not surprisingly, various RBPs, including Arpp21, Rbfox1, Lin28, Pumilio2, Staufen2, Elavl4, Ythdf, and FMRP, regulate the expression of mRNAs involved in synaptic transmission and neurite outgrowth. This directly serves as a link between RBPs, neuronal dysfunction, and occurrence of neurodevelopmental disorders ( Rehfeld et al, 2018 ; Vuong et al, 2018 ; Jang et al, 2019 ; Bowles et al, 2021 ; Schieweck et al, 2021 ; Sena et al, 2021 ; Worpenberg et al, 2021 ).…”

Section: Establishment Of the Unique Layered Structure Of The Neocortexmentioning

confidence: 99%

Evolution of the Neocortex Through RNA-Binding Proteins and Post-transcriptional Regulation

Salamon

Rašin

2022

Front. Neurosci.

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The human neocortex is undoubtedly considered a supreme accomplishment in mammalian evolution. It features a prenatally established six-layered structure which remains plastic to the myriad of changes throughout an organism’s lifetime. A fundamental feature of neocortical evolution and development is the abundance and diversity of the progenitor cell population and their neuronal and glial progeny. These evolutionary upgrades are partially enabled due to the progenitors’ higher proliferative capacity, compartmentalization of proliferative regions, and specification of neuronal temporal identities. The driving force of these processes may be explained by temporal molecular patterning, by which progenitors have intrinsic capacity to change their competence as neocortical neurogenesis proceeds. Thus, neurogenesis can be conceptualized along two timescales of progenitors’ capacity to (1) self-renew or differentiate into basal progenitors (BPs) or neurons or (2) specify their fate into distinct neuronal and glial subtypes which participate in the formation of six-layers. Neocortical development then proceeds through sequential phases of proliferation, differentiation, neuronal migration, and maturation. Temporal molecular patterning, therefore, relies on the precise regulation of spatiotemporal gene expression. An extensive transcriptional regulatory network is accompanied by post-transcriptional regulation that is frequently mediated by the regulatory interplay between RNA-binding proteins (RBPs). RBPs exhibit important roles in every step of mRNA life cycle in any system, from splicing, polyadenylation, editing, transport, stability, localization, to translation (protein synthesis). Here, we underscore the importance of RBP functions at multiple time-restricted steps of early neurogenesis, starting from the cell fate transition of transcriptionally primed cortical progenitors. A particular emphasis will be placed on RBPs with mostly conserved but also divergent evolutionary functions in neural progenitors across different species. RBPs, when considered in the context of the fascinating process of neocortical development, deserve to be main protagonists in the story of the evolution and development of the neocortex.

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“…As induced pluripotent stem cells (iPSCs) and new transgenic mouse lines become more readily available, it will be interesting to see whether and how these interactions occur in a stem cell context and within specific cell types of the brain and what effect they may have on development, neuronal function, and synaptic plasticity. Multiple papers have provided evidence regarding the importance of NF-κB in a variety of forms of neuronal plasticity and synapse development, however, it is only relatively recently that a link between the Lin28/let-7 pathway and neuronal plasticity has been observed [41,46,126,127]. As the interactions between NF-κB and the Lin28/let-7 pathway become more apparent, future research can be aimed at elucidating how these interactions impact the most critical features of brain development, neuroplastic function, and neural disorders.…”

Section: Conclusion Ongoing Questions Future Directionsmentioning

confidence: 99%

Multi-Level Regulatory Interactions between NF-κB and the Pluripotency Factor Lin28

Mills

Nassar

Ravindra

et al. 2020

Cells

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An appreciation for the complex interactions between the NF-κB transcription factor and the Lin28 RNA binding protein/let-7 microRNA pathways has grown substantially over the past decade. Both the NF-κB and Lin28/let-7 pathways are master regulators impacting cell survival, growth and proliferation, and an understanding of how interfaces between these pathways participate in governing pluripotency, progenitor differentiation, and neuroplastic responses remains an emerging area of research. In this review, we provide a concise summary of the respective pathways and focus on the function of signaling interactions at both the transcriptional and post-transcriptional levels. Regulatory loops capable of providing both reinforcing and extinguishing feedback have been described. We highlight convergent findings in disparate biological systems and indicate future directions for investigation.

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Persistent Lin28 Expression Impairs Neurite Outgrowth and Cognitive Function in the Developing Mouse Neocortex

Cited by 10 publications

References 47 publications

RNA-binding protein signaling in adult neurogenesis

RNA-binding protein signaling in adult neurogenesis

Evolution of the Neocortex Through RNA-Binding Proteins and Post-transcriptional Regulation

Multi-Level Regulatory Interactions between NF-κB and the Pluripotency Factor Lin28

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