Back to Search
Start Over
Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex
- Source :
- Neuron 103, 1086-1095.e5 (2019), Neuron
- Publication Year :
- 2019
- Publisher :
- Cell Press, 2019.
-
Abstract
- Summary Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent the position of astrocytes influences the fate of reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including the gray matter (GM) and white matter (WM), and targeted local reactive astrocytes via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors into mGFAP-Cre mice. Single proneural factors were not sufficient for adequate reprogramming, although their combination with the nuclear receptor-related 1 protein (Nurr1) improved reprogramming efficiency. Nurr1 and Neurogenin 2 (Ngn2) resulted in high-efficiency reprogramming of targeted astrocytes into neurons that develop lamina-specific hallmarks, including the appropriate long-distance axonal projections. Surprisingly, in the WM, we did not observe any reprogrammed neurons, thereby unveiling a crucial role of region- and layer-specific differences in astrocyte reprogramming.<br />Graphical Abstract<br />Highlights • AAV can be targeted to reactive astrocytes upon stab wound injury • Expression of Ngn2 and Nurr1 in these astrocytes induces pyramidal neurons • Induced pyramidal neurons acquire correct layer identity and axonal projections • Neurons cannot be induced in the white matter<br />Neurons dying after brain injury cannot be replaced. Mattugini, Bocchi, et al. show that local astrocytes can be converted into functional neurons acquiring appropriate layer identity and connectivity by expression of neurogenic factors in a mouse model of traumatic brain injury.
- Subjects :
- 0301 basic medicine
Genetic Vectors
Inflammation
Nerve Tissue Proteins
Wounds, Stab
Biology
Article
White matter
03 medical and health sciences
Mice
reactive gliosis
Aav
Astrocytes
Axonal Projection
Cerebral Cortex
Cortical Layers
Electrophysiology
Lentivirus
Reactive Gliosis
Reprogramming
0302 clinical medicine
lentivirus
Brain Injuries, Traumatic
Nuclear Receptor Subfamily 4, Group A, Member 2
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Cellular Reprogramming Techniques
Neurogenin-2
Gliosis
Gray Matter
Neurons
General Neuroscience
Pyramidal Cells
astrocytes
reprogramming
AAV
cortical layers
Dependovirus
electrophysiology
White Matter
030104 developmental biology
medicine.anatomical_structure
Cerebral cortex
inflammation
Mouse Cerebral Cortex
medicine.symptom
axonal projection
Neuroscience
030217 neurology & neurosurgery
Astrocyte
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neuron 103, 1086-1095.e5 (2019), Neuron
- Accession number :
- edsair.doi.dedup.....dece376b0f29c67b9ce96dd54e21ddc9