Motor neuron heterogeneity and vulnerability
Abstract/Contents
- Abstract
- The spinal cord is a fascinating structure that is responsible for coordinating movement in vertebrates. Spinal motor neurons control muscle activity by transmitting signals from the spinal cord to diverse peripheral targets in healthy adults. This biological process is disrupted in numerous neurodegenerative disorders, most notably amyotrophic lateral sclerosis (ALS). In ALS patients, motor neurons selectively detach from the muscles that they control and subsequently degenerate, causing sequential paralysis that culminates in death within 3-5 years. The key feature of ALS, as well as most other neurodegenerative diseases, is that it can be caused by mutations in numerous genes that are ubiquitously expressed throughout the central nervous system, yet the functional consequences of these mutations converge to induce similar cellular pathology and patient phenotypes. This phenomenon, known as selective vulnerability of neuronal subtypes, holds the key to understanding the molecular etiology of neurodegenerative disease. In the following work, we endeavored to uncover the core transcriptional differences that distinguish vulnerable and resistant neurons using a combination of single-cell transcriptomics, epigenetics, in situ hybridization, and mouse genetics. In the process, we identified unprecedented levels of transcriptional divergence throughout the healthy adult mouse motor system, including the discovery of functionally important subtypes of motor neurons, and described key gene expression differences that underlie their highly diversified function. Our characterization of the molecular machinery that enables neuronal control of the visceral and skeletal motor systems will provide a roadmap for future exploration of adult motor neuron function.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Blum, Jacob Aaron |
|---|---|
| Degree supervisor | Gitler, Aaron D |
| Thesis advisor | Gitler, Aaron D |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Reimer, Richard J |
| Degree committee member | Bassik, Michael |
| Degree committee member | Greenleaf, William James |
| Degree committee member | Reimer, Richard J |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jacob Aaron Blum. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/mt425mg4231 |
Access conditions
- Copyright
- © 2022 by Jacob Aaron Blum
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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