A Translational Repression Complex in Developing Mammalian Neural Stem Cells that Regulates Neuronal Specification

Zahr, Siraj K.; Yang, Guang; Kazan, Hilal; Borrett, Michael J.; Yuzwa, Scott A.; Voronova, Anastassia; Kaplan, David R.; Miller, Freda D.

doi:10.1016/j.neuron.2017.12.045

Cited by 130 publications

(163 citation statements)

References 39 publications

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“…S6 A-B) based on the presence of 315 known markers. Consistent with the previous finding (Zahr et al 2018), the RG and the IP 316 clusters express many layer marker genes (Supplemental Fig. S6B).…”

Section: Prdm16 Directly Represses Mid-layer Genes Including Fezf2 310supporting

confidence: 91%

PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

Jones

et al. 2019

Preprint

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36Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, 37 accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that 38 drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here we 39 reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early 40 to late phases of neurogenesis in the mouse neocortex. Prdm16 mutant RG delays the timely 41 progression of RG, leading to defective cortical laminar organization. We show that PRDM16 42 regulates expression of neuronal specification genes and a subset of genes that are dynamically 43 expressed between mid-and late-neurogenesis. Our genomic analysis suggests that PRDM16 44 suppresses target gene expression through maintaining chromatin accessibility of permissive 45 enhancers. Altogether, our results demonstrate a critical role of PRDM16 in establishing stage-46 specific gene expression program of RG during cortical neurogenesis. These findings also 47 support a model where progenitor cells are primed with daughter cell gene expression program 48 for rapid cell differentiation.

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Section: Prdm16 Directly Represses Mid-layer Genes Including Fezf2 310supporting

confidence: 91%

PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

Jones

et al. 2019

Preprint

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“…RBPs exploit different methods to block translation in RNP granules. Some recruit members of the 4E-BP family of proteins that bind eukaryotic translation initiation factor eIF4E and block translation during transit [23,24,25]. Some RBPs bind directly ribosomes and reversibly stall them while assembled on target mRNAs [26], whereas still others recruit de-adenylase proteins to shorten poly(A) tail length and prevent efficient binding of the cytosolic poly(A) binding proteins (PABPs) required for efficient translation initiation [27].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

Ravanidis

Kattan

Doxakis

2018

IJMS

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The timing, dosage and location of gene expression are fundamental determinants of brain architectural complexity. In neurons, this is, primarily, achieved by specific sets of trans-acting RNA-binding proteins (RBPs) and their associated factors that bind to specific cis elements throughout the RNA sequence to regulate splicing, polyadenylation, stability, transport and localized translation at both axons and dendrites. Not surprisingly, misregulation of RBP expression or disruption of its function due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to the pathogenesis of several neuropsychiatric and neurodegenerative disorders such as fragile-X syndrome, autism spectrum disorders, spinal muscular atrophy, amyotrophic lateral sclerosis and frontotemporal dementia. This review discusses the roles of Pumilio, Staufen, IGF2BP, FMRP, Sam68, CPEB, NOVA, ELAVL, SMN, TDP43, FUS, TAF15, and TIA1/TIAR in RNA metabolism by analyzing their specific molecular and cellular function, the neurological symptoms associated with their perturbation, and their axodendritic transport/localization along with their target mRNAs as part of larger macromolecular complexes termed ribonucleoprotein (RNP) granules.

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“…As such, the Pum2/E4‐T complex promotes translational repression of deep‐layer fate in upper‐layer neurons, thereby controlling correct temporal specification of newborn upper‐layer neurons (Zahr et al . ). It will be important in future studies to further elaborate whether or how Norad contributes to Pum2 target recognition and which exact role Norad exerts in generating cortical cell‐type diversity.…”

Section: Control Of Rgp Proliferation Behavior By Long Non‐coding Rnasmentioning

confidence: 97%

“…Cortical RGPs are transcriptionally primed to generate diverse types of neurons by simultaneously expressing mRNA of transcriptional regulators of both deep and superficial layer neurons. As such, the Pum2/E4-T complex promotes translational repression of deep-layer fate in upper-layer neurons, thereby controlling correct temporal specification of newborn upper-layer neurons (Zahr et al 2018). It will be important in future studies to further elaborate whether or how Norad contributes to Pum2 target recognition and which exact role Norad exerts in generating cortical cell-type diversity.…”

Section: Control Of Rgp Proliferation Behavior By Long Noncoding Rnasmentioning

confidence: 99%

Epigenetic cues modulating the generation of cell‐type diversity in the cerebral cortex

Amberg

Laukoter

Hippenmeyer

2018

Journal of Neurochemistry

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The cerebral cortex is composed of a large variety of distinct cell‐types including projection neurons, interneurons, and glial cells which emerge from distinct neural stem cell lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that neural stem cell and radial glial progenitor lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell‐type diversity during cortical development.

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A Translational Repression Complex in Developing Mammalian Neural Stem Cells that Regulates Neuronal Specification

Cited by 130 publications

References 39 publications

PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

Epigenetic cues modulating the generation of cell‐type diversity in the cerebral cortex

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