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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 08, 2017 |
| Title |
RNA-binding proteins Cugbp1 and HuD regulate neocortical projection neuron identities under the translational control of Neurotrophin-3 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Intrinsic molecular pathways in the central nervous system dictate neuronal cell fate during development. However, interplay of RNA binding proteins (RBPs) dictating mRNA translation, and their spatiotemporal extracellular regulators in neocortical neural stem cells during neurogenesis are poorly understood. Using an unbiased RNAseq screen of polysomes between early and mid-neurogenesis, we identified functionally related mRNA groups and their isoforms are regulated translationally in prenatal neocortices, including mRNAs encoding RBPs. Here, we show that isoforms of the RBP, Hu antigen D (HuD), regulate the balance of neocortical glutamatergic neurons in an isoform-specific manner during development. HuD3 promoted a Cdp+ intracortically projecting neuronal fate, while HuD4 promoted a Tle4+ subcortically projecting neuronal fate. In early neurogenic radial glia of the neocortex, HuD transcripts were bound and translationally repressed by another RBP, CUG triplet repeat RNA-binding protein 1 (Cugbp1). Cugbp1 knockdown increased the number of Cdp+ intracortically projecting neurons, while having distinct effects on Tle4+ and Ctip2+ subcortically projecting neurons. Neurotrophin-3 promoted HuD3 mRNA translation and Cdp+ fate, which was reversed by Cugbp1. Thus, our findings reveal a novel post-transcriptional molecular pathway in the developing neocortex that regulates the balance of distinct subpopulations of neocortical projection neurons.
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| Overall design |
Mouse neocortex from E13 and E16 were prepared and loaded onto sucrose density gradients. Fractions representing total cellular RNA, 40-60-80S, and polysome were sequenced using standard Illumina protocols.
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| Contributor(s) |
Kraushar ML, Hart RP, Rasin M |
| Citation(s) |
27296516, 32245946 |
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| Submission date |
Feb 06, 2016 |
| Last update date |
Apr 13, 2020 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
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| Phone |
848-445-1783
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| Organization name |
Rutgers University
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| Department |
Cell Biology & Neuroscience
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| Street address |
604 Allison Rd Rm B430
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| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA311125 |
| SRA |
SRP069743 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77647_isoformsFpkmMatrixRep.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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