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Series GSE229699 Query DataSets for GSE229699
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
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.
Overall design Comparative spatial transcriptomics of mouse brain sections obtained at E12 after either S. pneumoniae + ampicillin challenge or after ampicillin control.
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
Submission date Apr 13, 2023
Last update date Apr 16, 2023
Contact name Jeremy Chase Crawford
Organization name St. Jude Children's Research Hospital
Department Department of Host-Microbe Interactions
Street address MS 221, 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38105-3678
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
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
BioProject PRJNA955315

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Supplementary file Size Download File type/resource
GSE229699_RAW.tar 281.7 Mb (http)(custom) TAR (of H5, JSON, TIFF)
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Raw data are available in SRA
Processed data provided as supplementary file

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