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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 13, 2023 |
| Title |
Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function.
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| Overall design |
Comparative spatial transcriptomics of mouse brain sections obtained at E12 after either S. pneumoniae + ampicillin challenge or after ampicillin control.
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| Contributor(s) |
Crawford JC, Mann B, Tuomanen EI |
| Citation(s) |
37052506 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI128756 |
Bioactivities of pneumococcal cell wall in neuropathogenesis |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
Elaine I Tuomanen |
| R01 NS100939 |
Sonic Hedgehog signaling in neocortical growth and folding |
ST. JUDE CHILDREN'S RESEARCH HOSPITAL |
Young-Goo Han |
| U01 AI150747 |
DYNAMICS AND EVOLUTION OF IMMUNE RESPONSES TO INFLUENZA VIRUSES |
EMORY UNIVERSITY |
Paul G. Thomas |
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| Submission date |
Apr 13, 2023 |
| Last update date |
Apr 16, 2023 |
| Contact name |
Jeremy Chase Crawford |
| E-mail(s) |
jeremy.crawford@stjude.org
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| Organization name |
St. Jude Children's Research Hospital
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| Department |
Department of Host-Microbe Interactions
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| Street address |
MS 221, 262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105-3678 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM7173404 |
Mouse brain spatial transcriptomics, E12, ampicillin control, replicate 1 |
| GSM7173405 |
Mouse brain spatial transcriptomics, E12, S. pneumoniae + ampicillin challenge, replicate 1 |
| GSM7173406 |
Mouse brain spatial transcriptomics, E12, ampicillin control, replicate 2 |
| GSM7173407 |
Mouse brain spatial transcriptomics, E12, S. pneumoniae + ampicillin challenge, replicate 2 |
| GSM7173408 |
Mouse brain spatial transcriptomics, E12, ampicillin control, replicate 3 |
| GSM7173409 |
Mouse brain spatial transcriptomics, E12, S. pneumoniae + ampicillin challenge, replicate 3 |
| GSM7173410 |
Mouse brain spatial transcriptomics, E12, ampicillin control, replicate 4 |
| GSM7173411 |
Mouse brain spatial transcriptomics, E12, S. pneumoniae + ampicillin challenge, replicate 4 |
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| Relations |
| BioProject |
PRJNA955315 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229699_RAW.tar |
281.7 Mb |
(http)(custom) |
TAR (of H5, JSON, TIFF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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