| First Author | Kitt MM | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 3 | Pages | 110711 |
| PubMed ID | 35443166 | Mgi Jnum | J:326400 |
| Mgi Id | MGI:7284664 | Doi | 10.1016/j.celrep.2022.110711 |
| Citation | Kitt MM, et al. (2022) An adult-stage transcriptional program for survival of serotonergic connectivity. Cell Rep 39(3):110711 |
| abstractText | Neurons must function for decades of life, but how these non-dividing cells are preserved is poorly understood. Using mouse serotonin (5-HT) neurons as a model, we report an adult-stage transcriptional program specialized to ensure the preservation of neuronal connectivity. We uncover a switch in Lmx1b and Pet1 transcription factor function from controlling embryonic axonal growth to sustaining a transcriptomic signature of 5-HT connectivity comprising functionally diverse synaptic and axonal genes. Adult-stage deficiency of Lmx1b and Pet1 causes slowly progressing degeneration of 5-HT synapses and axons, increased susceptibility of 5-HT axons to neurotoxic injury, and abnormal stress responses. Axon degeneration occurs in a die back pattern and is accompanied by accumulation of alpha-synuclein and amyloid precursor protein in spheroids and mitochondrial fragmentation without cell body loss. Our findings suggest that neuronal connectivity is transcriptionally protected by maintenance of connectivity transcriptomes; progressive decay of such transcriptomes may contribute to age-related diseases of brain circuitry. |
