microRNA controls over cortical projection neuron development
Abstract/Contents
- Abstract
- Corticospinal motor neurons (CSMN), residing in layer V of the neocortex, are the brain component of the multi-neuron circuitry controlling voluntary movement in mammals. CSMN are closely related to deep layer callosal projection neurons (CPN) and have the same embryonic birthdate during development, however very different projection targets and functions. While several transcription factors important for specifying both CSMN and CPN have been identified, much of the molecular regulation of this process remains incompletely understood. MicroRNAs are post-transcriptional gene regulators that are ideally suited to control developmental programs, as multiple microRNAs can converge on multiple targets to repress translation. While microRNAs have been shown to play a role in the earliest stages of cortical development, their role in cortical projection neuron development and diversity is unknown. A differential microRNA expression analysis of CSMN vs. CPN revealed 19 microRNAs that are more highly expressed by CSMN vs. CPN at post-natal day 1 (P1) mouse. miR-409-3p, is enriched in CSMN compared to CPN at P1. Predicted gene targets of miR-409-3p include LMO4, a transcriptional regulator important for specifying CPN and associative projection neuron development. Gain- and loss-of function studies demonstrate that miR-409-3p can control cortical projection neuron fate in both embryonic cortical cultures, in part through repression of the CPN-expressed transcriptional regulator LMO4. In utero electroporation experiments during development demonstrate alteration in axon projection trajectory and projection neuron cell fate. Characterizing cluster-encoded microRNA controls on CSMN development may inform stem cell-based regenerative therapies for paralysis in clinically relevant conditions, including spinal cord injury.
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Diaz, Jessica Lynn |
|---|---|
| Degree supervisor | Palmer, Theo |
| Degree supervisor | Tharin, Suzanne |
| Thesis advisor | Palmer, Theo |
| Thesis advisor | Tharin, Suzanne |
| Thesis advisor | Buckmaster, Paul S |
| Thesis advisor | Sarnow, P. (Peter) |
| Degree committee member | Buckmaster, Paul S |
| Degree committee member | Sarnow, P. (Peter) |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jessica Lynn Diaz. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Jessica Lynn Diaz
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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