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| Status |
Public on Aug 07, 2023 |
| Title |
Mouse Celf4 cKO fetal neocortex polysome fractions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abnormalities in neocortical and synaptic development have been associated with neurodevelopmental disorders. However, the molecular and cellular mechanisms regulating the formation of the initial synapses in an evolutionary advanced neocortical layer, the subplate (SP), are poorly understood. Our snRNAseq screen of human prefrontal neocortices from early (11/12 PCW), mid (14/15 PCW) to late (17/18 PCW) fetal developmental stages revealed the bipartite-to-tripartite differentiation of SP neuronal subclasses. Using polysome profiling with RNAseq, we report for the first time a set of mRNAs undergoing translational control in cellular subclasses of developing human prefrontal neocortices, including SP neurons. By examining both mouse and human neocortex, we further found that an autism spectrum disorder (ASD)-risk gene and RNA binding protein CUGBP Elav-Like Family Member 4 (CELF4) is selectively expressed in the neurons of two synapse-enriched compartments, the SP and the marginal zone. Furthermore, CELF4 binds mRNA targets that are encoded by the synaptic genes associated with ASD and adverse neurodevelopmental outcomes; albeit in an evolutionarily advanced fashion between mouse and human synaptic mRNAs. The selective forebrain Celf4 deletion from developing mouse cortical neurons disrupts the balance of SP synapses in a gender-specific fashion. Taken together, our results underscore the importance of RNA binding proteins and mRNA translation in evolutionarily advanced synaptic development, as well as their possible contribution to gender specific protein synthesis and vulnerability.
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| Overall design |
Samples prepared from neocortex of mouse wild type or Celf4 conditional knockout (cKO) collected at P0 were fractionated on sucrose gradients to yield polysomes, monosomes and unfractionated input. The goal was to investigate regulation of translation by Celf4.
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| Contributor(s) |
Salamon I, Krsnik Z, Kostovic I, Hart RP, Rasin M |
| Citation(s) |
37758766 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 NS075367 |
Role of first neocortical RNA-Operon in specification of neocortical projection neurons |
RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY--RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL |
Mladen-Roko Rasin |
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| |
| Submission date |
Sep 28, 2022 |
| Last update date |
Nov 08, 2023 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
|
| Phone |
848-445-1783
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| Organization name |
Rutgers University
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| Department |
Cell Biology & Neuroscience
|
| Street address |
604 Allison Rd Rm B430
|
| 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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| This SubSeries is part of SuperSeries: |
| GSE214534 |
The role of mRNA translation in the synaptic development of prenatal mammalian neocortex |
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| Relations |
| BioProject |
PRJNA884999 |
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