| dc.contributor |
ERC - European Research Council |
|
| dc.contributor |
Wellcome Trust |
|
| dc.contributor |
EMBO - European Molecular Biology Organization |
|
| dc.contributor |
Simons Foundation Autism Research Initiative |
|
| dc.contributor |
Grant, Seth |
|
| dc.creator |
Tomas-Roca, Laura |
|
| dc.creator |
Qiu, Zhen |
|
| dc.creator |
Fransén, Erik |
|
| dc.creator |
Grant, Seth |
|
| dc.date |
2022-10-05T15:37:15Z |
|
| dc.date |
2022-10-05T15:37:15Z |
|
| dc.date.accessioned |
2023-02-17T20:52:37Z |
|
| dc.date.available |
2023-02-17T20:52:37Z |
|
| dc.identifier |
Tomas-Roca, Laura; Qiu, Zhen; Fransén, Erik; Grant, Seth. (2022). Pax6 Developmental Synaptome Atlas, [dataset]. University of Edinburgh, Centre for Clinical Brain Sciences. https://doi.org/10.7488/ds/3770. |
|
| dc.identifier |
https://hdl.handle.net/10283/4756 |
|
| dc.identifier |
https://doi.org/10.7488/ds/3770 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/244031 |
|
| dc.description |
Neurodevelopmental disorders of genetic origin delay the acquisition of normal abilities and cause disabling phenotypes. Nevertheless, spontaneous attenuation and even complete amelioration of symptoms in early childhood and adolescence can occur in many disorders, suggesting that brain circuits possess an intrinsic capacity to overcome the deficits arising from some germline mutations. We examined the molecular composition of almost a trillion excitatory synapses on a brain-wide scale between birth and adulthood in mice carrying a mutation in the homeobox transcription factor Pax6, a neurodevelopmental disorder model. Pax6 haploinsufficiency had no impact on total synapse number at any age. By contrast, the molecular composition of excitatory synapses, the postnatal expansion of synapse diversity and the acquisition of normal synaptome architecture were delayed in all brain regions, interfering with networks and electrophysiological simulations of cognitive functions. Specific excitatory synapse types and subtypes were affected in two key developmental age-windows. These phenotypes were reversed within 2-3 weeks of onset, restoring synapse diversity and synaptome architecture to the normal developmental trajectory. Synapse subtypes with rapid protein turnover mediated the synaptome remodeling. This brain-wide capacity for remodeling of synapse molecular composition to recover and maintain the developmental trajectory of synaptome architecture may help confer resilience to neurodevelopmental genetic disorders. |
|
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application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
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| dc.format |
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
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| dc.format |
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
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application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
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application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
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application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
|
| dc.format |
text/plain |
|
| dc.language |
eng |
|
| dc.publisher |
University of Edinburgh, Centre for Clinical Brain Sciences |
|
| dc.relation |
https://doi.org/10.1101/2021.12.21.473638 |
|
| dc.relation |
Developmental resilience of synaptome architecture Laura Tomas-Roca, Zhen Qiu, Erik Fransén, Ragini Gokhale, Edita Bulovaite, David J. Price, Noboru H. Komiyama, Seth G.N. Grant bioRxiv 2021.12.21.473638; doi: https://doi.org/10.1101/2021.12.21.473638 This article is a preprint and has not been certified by peer review |
|
| dc.relation |
https://doi.org/10.7488/ds/3264 |
|
| dc.rights |
Creative Commons Attribution 4.0 International Public License |
|
| dc.subject |
Pax6 |
|
| dc.subject |
Synapse |
|
| dc.subject |
brain atlas |
|
| dc.subject |
synaptome |
|
| dc.subject |
canalisation |
|
| dc.subject |
Neurodevelopmental disorder |
|
| dc.subject |
Autism |
|
| dc.subject |
Intellectual disability |
|
| dc.subject |
Biological Sciences::Developmental Biology |
|
| dc.title |
Pax6 Developmental Synaptome Atlas |
|
| dc.title |
Developmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model |
|
| dc.type |
dataset |
|
| dc.coverage |
Edinburgh |
|
| dc.coverage |
UK |
|
| dc.coverage |
UNITED KINGDOM |
|