Mechanism of non-neuronal fate repression during C. elegans neurogenesis
Abstract/Contents
- Abstract
- Cellular differentiation is defined by tuning of the cell's transcriptional program into its target. Examples of developmental repressors such as REST suggest that non-target programs need to be repressed in parallel to activating the target programs. While it is well established that proneural genes activate neuronal transcription programs, little is known about how differentiating neurons repress non-neuronal programs to ensure neuronal fates. Myt1 family factors are transcriptional repressors that contribute to neuronal reprogramming from non-neuronal cells in vitro, but their function during neuronal differentiation remain unclear. In this dissertation, I characterize the sole C. elegans Myt1 family ortholog ZTF-11. We show that ZTF-11 is required for neurogenesis in multiple neuronal lineages from previously differentiated epithelial cells, including a neuron generated from a developmental neuronal transdifferentiation event. ZTF-11 is exclusively expressed in all neuronal precursors with remarkable specificity at single cell resolution, likely through direct activation by proneural genes. ZTF-11 is required to eliminate epithelial identity from neurons generated from epithelial precursors. In these neurons, loss of ztf-11 results in loss of neuronal identity. Ectopic expression of ZTF-11 is sufficient to generate additional neurons through repressing epithelial identity. In contrast, neurons generated from dedicated neuronal lineages are still generated without ZTF-11, suggesting that neurons face different developmental challenges from non-neuronal programs. Loss of ztf-11 results in upregulation of many non-neuronal genes. ZTF-11 functions together with MuvB corepressor complex to repress its target genes. These results provides insights on the ability of Myt1l to drive neuronal transdifferentiation in vitro as well as the developmental role of Myt1 family factors. Taken together, I identify an evolutionarily conserved mechanism to specify neuronal fates by repressing non-neuronal genes.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lee, Joo | |
|---|---|---|
| Degree supervisor | Shen, Kang, 1972- | |
| Thesis advisor | Shen, Kang, 1972- | |
| Thesis advisor | Krasnow, Mark, 1956- | |
| Thesis advisor | Rohatgi, Rajat | |
| Thesis advisor | Straight, Aaron, 1966- | |
| Degree committee member | Krasnow, Mark, 1956- | |
| Degree committee member | Rohatgi, Rajat | |
| Degree committee member | Straight, Aaron, 1966- | |
| Associated with | Stanford University, Department of Biochemistry. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joo Lee. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Joo Lee
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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